UGT1A1

Summary

Gene Symbol: UGT1A1
Description: UDP glucuronosyltransferase family 1 member A1
Alias: BILIQTL1, GNT1, HUG-BR1, UDPGT, UDPGT 1-1, UGT1, UGT1A, UDP-glucuronosyltransferase 1-1, UDP glucuronosyltransferase 1 family, polypeptide A1, UDP glycosyltransferase 1 family, polypeptide A1, UDP-glucuronosyltransferase 1-A, UDP-glucuronosyltransferase 1A1, UGT-1A, UGT1*1, UGT1-01, UGT1.1, bilirubin UDP-glucuronosyltranserase, bilirubin UDP-glucuronosyltransferase 1-1, bilirubin UDP-glucuronosyltransferase isozyme 1, bilirubin-specific UDPGT isozyme 1
Species: human
Products:     UGT1A1

Top Publications

  1. Kweekel D, Gelderblom H, van der Straaten T, Antonini N, Punt C, Guchelaar H. UGT1A1*28 genotype and irinotecan dosage in patients with metastatic colorectal cancer: a Dutch Colorectal Cancer Group study. Br J Cancer. 2008;99:275-82 pubmed publisher
    The aim of the study was to investigate the associations between UGT1A1(*)28 genotype and (1) response rates, (2) febrile neutropenia and (3) dose intensity in patients with metastatic colorectal cancer treated with irinotecan...
  2. Huang Y, Huang M, Yang S, Teng H, Huang C. Variations in the UDP-glucuronosyltransferase 1A1 gene for the development of unconjugated hyperbilirubinemia in Taiwanese. Pharmacogenomics. 2008;9:1229-35 pubmed publisher
    ..length polymorphism was utilized to determine variants at nucleotides -3279 (*60), -53 (*28) and 211 (*6) in the UGT1A1 gene for 178 Taiwanese hyperbilirubinemic patients and 200 controls...
  3. Saito Y, Sai K, Maekawa K, Kaniwa N, Shirao K, Hamaguchi T, et al. Close association of UGT1A9 IVS1+399C>T with UGT1A1*28, *6, or *60 haplotype and its apparent influence on 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronidation in Japanese. Drug Metab Dispos. 2009;37:272-6 pubmed publisher
    ..99) and UGT1A1*6 (211G>A, 0.86), in moderate LD with UGT1A1*60 (-3279T>G, 0...
  4. Braun M, Richman S, Thompson L, Daly C, Meade A, Adlard J, et al. Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial. J Clin Oncol. 2009;27:5519-28 pubmed publisher
    ..DPYD), methylenetetrahydrofolate reductase (MTHFR), mutL homolog 1 (MLH1), UDP glucuronyltransferase (UGT1A1), ATP-binding cassette group B gene 1 (ABCB1), x-ray cross-complementing group 1 (XRCC1), glutathione-S-..
  5. Vasavda N, Menzel S, Kondaveeti S, Maytham E, Awogbade M, Bannister S, et al. The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease. Br J Haematol. 2007;138:263-70 pubmed
    ..SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent...
  6. Cox A, Ng M, Xu J, Langefeld C, Koch K, Dawson P, et al. Association of SNPs in the UGT1A gene cluster with total bilirubin and mortality in the Diabetes Heart Study. Atherosclerosis. 2013;229:155-60 pubmed publisher
    ..In addition, TBili is thought to be under strong genetic regulation via the UGT1A gene family, suggesting it may be a heritable CVD risk factor...
  7. Melton P, Haack K, Göring H, Laston S, Umans J, Lee E, et al. Genetic influences on serum bilirubin in American Indians: The Strong Heart Family Study. Am J Hum Biol. 2011;23:118-25 pubmed publisher
    ..Genetic variation within the promoter region of uridine diphosphate glucuronosyltransferase (UGT1A1) on chromosome 2q has been associated with elevated serum bilirubin levels in European populations...
  8. Schulz C, Heinemann V, Schalhorn A, Moosmann N, Zwingers T, Boeck S, et al. UGT1A1 gene polymorphism: impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer. World J Gastroenterol. 2009;15:5058-66 pubmed
    To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC)..
  9. Inoue K, Sonobe M, Kawamura Y, Etoh T, Takagi M, Matsumura T, et al. Polymorphisms of the UDP-glucuronosyl transferase 1A genes are associated with adverse events in cancer patients receiving irinotecan-based chemotherapy. Tohoku J Exp Med. 2013;229:107-14 pubmed
    ..and multivariate analysis of patients' physiological and genetic factors revealed that one or more genotypes of UGT1A1*6/*28, UGT1A7*3/*3, and UGT1A9*1/*1 may enhance the adverse events...

More Information

Publications100

  1. Lin R, Wang X, Wang Y, Zhang F, Wang Y, Fu W, et al. Association of polymorphisms in four bilirubin metabolism genes with serum bilirubin in three Asian populations. Hum Mutat. 2009;30:609-15 pubmed publisher
    Numerous studies have shown that the (TA)n repeat polymorphism in the uridine diphosphate glycosyltransferase 1 (UGT1A1) gene promoter is associated with hyperbilirubinemia...
  2. Sugatani J, Nishitani S, Yamakawa K, Yoshinari K, Sueyoshi T, Negishi M, et al. Transcriptional regulation of human UGT1A1 gene expression: activated glucocorticoid receptor enhances constitutive androstane receptor/pregnane X receptor-mediated UDP-glucuronosyltransferase 1A1 regulation with glucocorticoid receptor-interacting p. Mol Pharmacol. 2005;67:845-55 pubmed
    ..the phenobarbital response activity to a 290-base pair (bp) distal enhancer sequence (-3499/-3210) of the human UGT1A1 gene that is activated by the constitutive androstane receptor (CAR)...
  3. Zhou Y, Lee L, Ng S, Hia C, Low K, Chong Y, et al. UGT1A1 haplotype mutation among Asians in Singapore. Neonatology. 2009;96:150-5 pubmed publisher
    The uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) enzyme is responsible for conjugation of the bilirubin in the liver as well as for drug metabolism...
  4. Mathijssen R, de Jong F, van Schaik R, Lepper E, Friberg L, Rietveld T, et al. Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. J Natl Cancer Inst. 2004;96:1585-92 pubmed
    ..metabolize irinotecan, including cytochrome P450 3A4 (CYP3A4) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1)...
  5. Kang T, Kim H, Ju H, Kim J, Jeon Y, Lee H, et al. Genome-wide association of serum bilirubin levels in Korean population. Hum Mol Genet. 2010;19:3672-8 pubmed publisher
    ..Significant associations were observed at UGT1A1 (rs11891311, P = 4.78 x 10(-148)) and SLCO1B3 (rs2417940, P = 1...
  6. Ramchandani R, Wang Y, Booth B, Ibrahim A, Johnson J, Rahman A, et al. The role of SN-38 exposure, UGT1A1*28 polymorphism, and baseline bilirubin level in predicting severe irinotecan toxicity. J Clin Pharmacol. 2007;47:78-86 pubmed
    ..The objective of this analysis was to evaluate the role of SN-38 exposure, the active metabolite of irinotecan, UGT1A1 genotypes, and baseline bilirubin on the maximum decrease (nadir) in absolute neutrophil counts following ..
  7. Boo N, Wong F, Wang M, Othman A. Homozygous variant of UGT1A1 gene mutation and severe neonatal hyperbilirubinemia. Pediatr Int. 2009;51:488-93 pubmed publisher
    ..prevalence of nucleotide 211 guanine to adenine (G-->A) mutation of uridine diphosphoglucuronosyl transferase (UGT1A1) gene in Malaysian Chinese newborns with and without severe hyperbilirubinemia (total serum bilirubin >250 ..
  8. Boige V, Mendiboure J, Pignon J, Loriot M, Castaing M, Barrois M, et al. Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05. J Clin Oncol. 2010;28:2556-64 pubmed publisher
    ..Twenty polymorphisms within the DPD, TS, MTHFR, ERCC1, ERCC2, GSTP1, GSTM1, GSTT1, and UGT1A1 genes were genotyped...
  9. Park S, Kong S, Rhee J, Park Y, Ryu K, Lee J, et al. Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results. Ann Oncol. 2011;22:890-6 pubmed publisher
    ..UGT1A polymorphisms were associated with significantly higher incidence of grade 4 leukopenia (UGT1A1*6), neutropenia (UGT1A1*6, UGT1A6*2, and UGT1A7*3), grade 3/4 febrile neutropenia (UGT1A1*6), and grade 3 ..
  10. Karatzas A, Giannatou E, Tzortzis V, Gravas S, Aravantinos E, Moutzouris G, et al. Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and prostate cancer risk in Caucasian men. Cancer Epidemiol. 2010;34:345-9 pubmed publisher
    ..Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is a main metabolic pathway of estrogen detoxification in steroid target tissues, such as the prostate...
  11. Pacheco P, Brilhante M, Ballart C, Sigalat F, Polena H, Cabral R, et al. UGT1A1, UGT1A6 and UGT1A7 genetic analysis: repercussion for irinotecan pharmacogenetics in the São Miguel Island Population (Azores, Portugal). Mol Diagn Ther. 2009;13:261-8 pubmed publisher
    ..São Miguel Island (Azores, Portugal) in order to determine the frequencies of polymorphisms and haplotypes in UGT1A1, UGT1A6, and UGT1A7, the co-occurrence of reduced enzyme activity UGT1A variants related to irinotecan toxicity, ..
  12. de Jong F, Kehrer D, Mathijssen R, Creemers G, de Bruijn P, van Schaik R, et al. Prophylaxis of irinotecan-induced diarrhea with neomycin and potential role for UGT1A1*28 genotype screening: a double-blind, randomized, placebo-controlled study. Oncologist. 2006;11:944-54 pubmed
    ..Baseline patient characteristics, systemic SN-38 exposure, and UGT1A1*28 genotype status (i.e...
  13. Chaouch L, Said Y, Moumni I, Mahjoubi I, Chaabene A, Darragi I, et al. Implication of genetic variation at the promoter and exon1 of UGT1A1 in occurrence of cholelithiasis in Tunisia. Ann Biol Clin (Paris). 2012;70:702-6 pubmed publisher
    Bilirubin is conjugated with glucoronic acid in the liver by UDP-glucuronosyltransferase 1A1 (UGT1A1)...
  14. Martinez Balibrea E, Abad A, Martinez Cardus A, Gines A, Valladares M, Navarro M, et al. UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy. Br J Cancer. 2010;103:581-9 pubmed publisher
    ..Genotyping of TYMS (5'TRP and 3'UTR), UGT1A1(*)28, UGT1A9(*)22 and UGT1A7(*)3 was performed in 149 metastatic CRC patients treated with irinotecan/5FU as first-..
  15. Glimelius B, Garmo H, Berglund A, Fredriksson L, Berglund M, Kohnke H, et al. Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer. Pharmacogenomics J. 2011;11:61-71 pubmed publisher
    ..Irinotecan's active metabolite is inactivated by UDP-glucuronosyltransferase 1A1 (UGT1A1), which is deficient in Gilbert's syndrome...
  16. Dias M, McKinnon R, Sorich M. Impact of the UGT1A1*28 allele on response to irinotecan: a systematic review and meta-analysis. Pharmacogenomics. 2012;13:889-99 pubmed publisher
    Pre-emptive irinotecan dose reduction for UGT1A1*28 homozygotes may result in reduced risk of severe neutropenia and diarrhea...
  17. Strassburg C, Lankisch T, Manns M, Ehmer U. Family 1 uridine-5'-diphosphate glucuronosyltransferases (UGT1A): from Gilbert's syndrome to genetic organization and variability. Arch Toxicol. 2008;82:415-33 pubmed publisher
    ..Glucuronidation and its variability are likely to represent an important factor for individualized drug therapy and risk prediction impacting the drug development and licensing processes. ..
  18. Fujita K, Ando Y, Nagashima F, Yamamoto W, Eodo H, Araki K, et al. Genetic linkage of UGT1A7 and UGT1A9 polymorphisms to UGT1A1*6 is associated with reduced activity for SN-38 in Japanese patients with cancer. Cancer Chemother Pharmacol. 2007;60:515-22 pubmed
    ..at -57 and UGT1A7*2 to *9), UGT1A9 (9 or 10 repeat of T at -118 [-118(T)9 or 10] and UGT1A9*2 to *5), and UGT1A1 (UGT1A1*6, UGT1A1*27, and UGT1A1*28) were analyzed for all patients...
  19. Bielinski S, Chai H, Pathak J, Talwalkar J, Limburg P, Gullerud R, et al. Mayo Genome Consortia: a genotype-phenotype resource for genome-wide association studies with an application to the analysis of circulating bilirubin levels. Mayo Clin Proc. 2011;86:606-14 pubmed publisher
    ..1 × 10(-8)) corresponding to a gene cluster of uridine 5'-diphospho-glucuronosyltransferases (the UGT1A cluster) and solute carrier organic anion transporter family, member 1B1 (SLCO1B1), respectively...
  20. Teng H, Huang M, Tang K, Yang S, Tseng C, Huang C. Combined UGT1A1 and UGT1A7 variant alleles are associated with increased risk of Gilbert's syndrome in Taiwanese adults. Clin Genet. 2007;72:321-8 pubmed
    ..This reduction is associated with UGT1A1*28 and UGT1A1*6 polymorphisms...
  21. Huo D, Kim H, Adebamowo C, Ogundiran T, Akang E, Campbell O, et al. Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and breast cancer risk in Africans. Breast Cancer Res Treat. 2008;110:367-76 pubmed
    The UDP-glucuronosylatransferase 1A1 (UGT1A1) gene is involved in the metabolism of estrogen and detoxification of potential carcinogens...
  22. Buch S, Schafmayer C, Volzke H, Seeger M, Miquel J, Sookoian S, et al. Loci from a genome-wide analysis of bilirubin levels are associated with gallstone risk and composition. Gastroenterology. 2010;139:1942-1951.e2 pubmed publisher
    ..Bilirubin is a major component of gallstones so we investigated whether these variants predict gallstone bilirubin content and overall risk for gallstones...
  23. Massacesi C, Terrazzino S, Marcucci F, Rocchi M, Lippe P, Bisonni R, et al. Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy. Cancer. 2006;106:1007-16 pubmed
    ..evaluated the association between genomic polymorphic variants in uridine diphosphate glucuronosyl transferase (UGT1A1), methylenetetrahydrofolate reductase (MTHFR), and thymidylate synthase (TS) genes, and the incidence of the ..
  24. Girard H, Levesque E, Bellemare J, Journault K, Caillier B, Guillemette C. Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activity. Pharmacogenet Genomics. 2007;17:1077-89 pubmed
    ..molecular weight of approximately 45 kDa were confirmed in microsomes of human tissues using antibodies against UGT1A1 and anti-UGT1A7/8/9/10...
  25. Tang K, Chiu H, Chen H, Eng H, Tsai C, Teng H, et al. Link between colorectal cancer and polymorphisms in the uridine-diphosphoglucuronosyltransferase 1A7 and 1A1 genes. World J Gastroenterol. 2005;11:3250-4 pubmed
    ..between single nucleotide polymorphisms in the uridine-diphosphoglucuronosyltransferase (UGT) UGT1A7 and UGT1A1 genes and patients suffering from colorectal cancer (CRC)...
  26. Kanai M, Kijima K, Shirahata E, Sasaki A, Akaba K, Umetsu K, et al. Neonatal hyperbilirubinemia and the bilirubin uridine diphosphate-glucuronosyltransferase gene: the common -3263T > G mutation of phenobarbital response enhancer module is not associated with the neonatal hyperbilirubinemia in Japanese. Pediatr Int. 2005;47:137-41 pubmed
    ..G71R) mutation of the bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1) gene causing Gilbert syndrome...
  27. Chen Y, Hung S, Tarng D. Serum bilirubin links UGT1A1*28 polymorphism and predicts long-term cardiovascular events and mortality in chronic hemodialysis patients. Clin J Am Soc Nephrol. 2011;6:567-74 pubmed publisher
    ..degradation is mainly determined by the activity of hepatic bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1), which is significantly influenced by a TA-repeat polymorphism in the gene's promoter, an allele designated ..
  28. Sanna S, Busonero F, Maschio A, McArdle P, Usala G, Dei M, et al. Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia. Hum Mol Genet. 2009;18:2711-8 pubmed publisher
    ..Unconjugated bilirubin is transported into hepatocytes. There, it is glucuronidated by UGT1A1 and secreted into the bile canaliculi...
  29. Mercke Odeberg J, Andrade J, Holmberg K, Hoglund P, Malmqvist U, Odeberg J. UGT1A polymorphisms in a Swedish cohort and a human diversity panel, and the relation to bilirubin plasma levels in males and females. Eur J Clin Pharmacol. 2006;62:829-37 pubmed
    ..Haplotype analysis of the UGT1A1 (*1*28), UGT1A6 (*1*2), and UGT1A7(*1*2*3*4) allelic variants showed that three major haplotypes constituted 84% ..
  30. Carpenter S, Lieff S, Howard T, Eggleston B, Ware R. UGT1A1 promoter polymorphisms and the development of hyperbilirubinemia and gallbladder disease in children with sickle cell anemia. Am J Hematol. 2008;83:800-3 pubmed publisher
    ..A total of 324 children with HbSS (median age 6.9 years) had UGT1A1 genotyping; 243 (75%) had common (TA)(6) or (TA)(7) alleles, whereas 81 (25...
  31. Innocenti F, Kroetz D, Schuetz E, Dolan M, Ramirez J, Relling M, et al. Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics. J Clin Oncol. 2009;27:2604-14 pubmed publisher
    We aim to identify genetic variation, in addition to the UGT1A1*28 polymorphism, that can explain the variability in irinotecan (CPT-11) pharmacokinetics and neutropenia in cancer patients...
  32. Huang C, Dulau A, Su Rick C, Pan Q. Validation of rapid polymerase chain reaction-based detection of all length polymorphisms in the UGT 1A1 gene promoter. Diagn Mol Pathol. 2007;16:50-3 pubmed
    ..of an insertion of a TA nucleotide sequence into a (TA)6TAA sequence in the gene promoter resulting in (TA)7TAA (UGT1A1*28)...
  33. Italia K, Jijina F, Jain D, Merchant R, Nadkarni A, Mukherjee M, et al. The effect of UGT1A1 promoter polymorphism on bilirubin response to hydroxyurea therapy in hemoglobinopathies. Clin Biochem. 2010;43:1329-32 pubmed publisher
    ..However, the effect of hydroxyurea on hyperbilirubinemia in relation to the UGT1A1 gene promoter polymorphism is not known in Indian patients with different hemoglobinopathies.
  34. Sneitz N, Bakker C, de Knegt R, Halley D, Finel M, Bosma P. Crigler-Najjar syndrome in The Netherlands: identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutants. Hum Mutat. 2010;31:52-9 pubmed publisher
    Crigler-Najjar syndrome (CN), caused by deficiency of UGT isoform 1A1 (UGT1A1), is characterized by severe unconjugated hyperbilirubinemia...
  35. Chou H, Chen M, Yang H, Su Y, Hsieh W, Chen C, et al. 211 G to a variation of UDP-glucuronosyl transferase 1A1 gene and neonatal breastfeeding jaundice. Pediatr Res. 2011;69:170-4 pubmed publisher
    ..The uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphism was shown to contribute to the development of neonatal hyperbilirubinemia...
  36. Ostanek B, Furlan D, Mavec T, Lukac Bajalo J. UGT1A1(TA)n promoter polymorphism--a new case of a (TA)8 allele in Caucasians. Blood Cells Mol Dis. 2007;38:78-82 pubmed
    ..hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin UDP-glucuronosyltransferase gene (UGT1A1)...
  37. Farheen S, Sengupta S, Santra A, Pal S, Dhali G, Chakravorty M, et al. Gilbert's syndrome: High frequency of the (TA)7 TAA allele in India and its interaction with a novel CAT insertion in promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 gene. World J Gastroenterol. 2006;12:2269-75 pubmed
    To identify the variants in UDP-glucuronosyltransferase 1 (UGT1A1) gene in Gilbert's syndrome (GS) and to estimate the association between homozygosity for TA insertion and GS in India, as well as the frequency of TA insertion and its ..
  38. Han J, Lim H, Shin E, Yoo Y, Park Y, Lee J, et al. Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol. 2006;24:2237-44 pubmed
    ..All statistical tests were two-sided. In genotype-PK association analysis, UGT1A1*6/*6 (n = 6), UGT1A7*3/*3 (n = 6), and UGT1A9-118(dT)9/9 (n = 11) were associated with significantly lower area ..
  39. Nikolac N, Simundic A, Topic E, Jurcic Z, Stefanovic M, Dumic J, et al. Rare TA repeats in promoter TATA box of the UDP glucuronosyltranferase (UGT1A1) gene in Croatian subjects. Clin Chem Lab Med. 2008;46:174-8 pubmed publisher
    ..or recurrent mild unconjugated hyperbilirubinemia caused by decreased activity of UDP glucuronosyltranferase (UGT1A1)...
  40. Hazama S, Nagashima A, Kondo H, Yoshida S, Shimizu R, Araki A, et al. Phase I study of irinotecan and doxifluridine for metastatic colorectal cancer focusing on the UGT1A1*28 polymorphism. Cancer Sci. 2010;101:722-7 pubmed publisher
    Although individuals carrying the UGT1A1 allele *28 have an increased risk of severe toxicities associated with irinotecan, no phase I study has been conducted based on the polymorphism...
  41. Singer J, Shou Y, Giles F, Kantarjian H, Hsu Y, Robeva A, et al. UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia. Leukemia. 2007;21:2311-5 pubmed
    ..Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) glucuronidates bilirubin in humans, and a polymorphism in the promoter of the gene that encodes it has been ..
  42. Cote J, Kirzin S, Kramar A, Mosnier J, Diebold M, Soubeyran I, et al. UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. Clin Cancer Res. 2007;13:3269-75 pubmed
    ..was extracted and genotyped to detect nucleotide polymorphism: 3435C>T for ABCB1, 6986A>G for CYP3A5, UGT1A1*28 and -3156G>A for UGT1A1. Genotype frequencies were similar in both treatment arms...
  43. Toffoli G, Cecchin E, Corona G, Russo A, Buonadonna A, D Andrea M, et al. The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer. J Clin Oncol. 2006;24:3061-8 pubmed
    b>UGT1A1*28 polymorphism has been associated with decreased glucuronidation of SN38, the active metabolite of irinotecan. This could increase toxicity with this agent...
  44. Schwertner H, Vitek L. Gilbert syndrome, UGT1A1*28 allele, and cardiovascular disease risk: possible protective effects and therapeutic applications of bilirubin. Atherosclerosis. 2008;198:1-11 pubmed publisher
    ..and the possible protective roles of bilirubin, heme oxygenase (HO), and bilirubin UDP-glucuronosyltransferase (UGT1A1)...
  45. Sugatani J, Mizushima K, Osabe M, Yamakawa K, Kakizaki S, Takagi H, et al. Transcriptional regulation of human UGT1A1 gene expression through distal and proximal promoter motifs: implication of defects in the UGT1A1 gene promoter. Naunyn Schmiedebergs Arch Pharmacol. 2008;377:597-605 pubmed publisher
    ..A 290-bp distal enhancer module, phenobarbital-responsive enhancer module of UGT1A1 (gtPBREM), fully accounts for constitutive androstane receptor (CAR)-, pregnane X receptor (PXR)-, glucocorticoid ..
  46. Onoue M, Terada T, Kobayashi M, Katsura T, Matsumoto S, Yanagihara K, et al. UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients. Int J Clin Oncol. 2009;14:136-42 pubmed publisher
    Gene polymorphisms of the UDP-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) contribute to individual variations in adverse events among patients administered irinotecan, and the distribution of the polymorphisms shows large ..
  47. Lin J, O Donnell C, Schwaiger J, Cupples L, Lingenhel A, Hunt S, et al. Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart Study. Circulation. 2006;114:1476-81 pubmed
    ..A candidate gene in the linkage region encodes hepatic bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1). The insertion of a TA in the TATAA box of the gene, an allele designated UGT1A1*28, decreases gene transcription...
  48. Peterkin V, Bauman J, Goosen T, Menning L, Man M, Paulauskis J, et al. Limited influence of UGT1A1*28 and no effect of UGT2B7*2 polymorphisms on UGT1A1 or UGT2B7 activities and protein expression in human liver microsomes. Br J Clin Pharmacol. 2007;64:458-68 pubmed
    b>UGT1A1 and UGT2B7 are enzymes that commonly contribute to drug glucuronidation...
  49. Braun M, Richman S, Quirke P, Daly C, Adlard J, Elliott F, et al. Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial. J Clin Oncol. 2008;26:2690-8 pubmed publisher
    ..MGMT), and cyclooxygenase 2 (COX2); germline DNA polymorphisms in GSTP1, ABCB1, XRCC1, ERCC2, and UGT1A1. These were screened in more than 750 patients for interaction with benefit from irinotecan or oxaliplatin; two ..
  50. Chaar V, Keclard L, Diara J, Leturdu C, Elion J, Krishnamoorthy R, et al. Association of UGT1A1 polymorphism with prevalence and age at onset of cholelithiasis in sickle cell anemia. Haematologica. 2005;90:188-99 pubmed
    ..in SCA was associated with the promoter polymorphism of the 5?-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) gene encoding a key enzyme in bilirubin catabolism...
  51. Agrawal S, Kumar P, Rathi R, Sharma N, Das R, Prasad R, et al. UGT1A1 gene polymorphisms in North Indian neonates presenting with unconjugated hyperbilirubinemia. Pediatr Res. 2009;65:675-80 pubmed publisher
    ..TA)n promoter polymorphism and Gly71Arg mutation in uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene in neonates > or =35-wk gestation presenting with bilirubin levels > or =18 mg/dL and controls, 2) ..
  52. Kaniwa N, Kurose K, Jinno H, Tanaka Kagawa T, Saito Y, Saeki M, et al. Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686C> T (P229L) found in an African-American. Drug Metab Dispos. 2005;33:458-65 pubmed
    Ethnic differences in genetic polymorphisms in UDP-glucuronosyltransferase 1A1 (UGT1A1) were investigated among African-Americans, Caucasians, and Japanese using samples obtained from 150 individuals for each population...
  53. Borucki K, Weikert C, Fisher E, Jakubiczka S, Luley C, Westphal S, et al. Haplotypes in the UGT1A1 gene and their role as genetic determinants of bilirubin concentration in healthy German volunteers. Clin Biochem. 2009;42:1635-41 pubmed publisher
    Genetic variations of UDP-glucuronyltransferase 1A1 (UGT1A1) influence the concentration of serum bilirubin...
  54. Long J, Zhang S, Fang X, Luo Y, Liu J. Association of neonatal hyperbilirubinemia with uridine diphosphate-glucuronosyltransferase 1A1 gene polymorphisms: meta-analysis. Pediatr Int. 2011;53:530-40 pubmed publisher
    ..factors, including mutations in the coding region or promoter of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) may increase the risk of development of neonatal hyperbilirubinemia, but the relationship has not been evaluated ..
  55. Johnson A, Kavousi M, Smith A, Chen M, Dehghan A, Aspelund T, et al. Genome-wide association meta-analysis for total serum bilirubin levels. Hum Mol Genet. 2009;18:2700-10 pubmed publisher
    ..Meta-analysis showed strong replication for a genetic influence on serum bilirubin levels of the UGT1A1 locus (P < 5 x 10(-324)) and a 12p12.2 locus. The peak signal in the 12p12...
  56. Lin J, Schwaiger J, Cupples L, O Donnell C, Zheng G, Schoenborn V, et al. Conditional linkage and genome-wide association studies identify UGT1A1 as a major gene for anti-atherogenic serum bilirubin levels--the Framingham Heart Study. Atherosclerosis. 2009;206:228-33 pubmed publisher
    ..studies we identified a major locus on chromosome 2q harboring the candidate gene UDP-glucuronosyltransferase (UGT1A1). The activity of this enzyme is significantly influenced by a TA-repeat polymorphism in the promoter of the gene...
  57. Cecchin E, Innocenti F, D Andrea M, Corona G, De Mattia E, Biason P, et al. Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan. J Clin Oncol. 2009;27:2457-65 pubmed publisher
    b>UGT1A1*28 is considered the main pharmacogenetic predictor of the toxicity outcome of irinotecan-treated patients...
  58. Romero R, Morales R, Garcia F, Huarriz M, Bandres E, de la Haba J, et al. Potential application of GSTT1-null genotype in predicting toxicity associated to 5-fluouracil irinotecan and leucovorin regimen in advanced stage colorectal cancer patients. Oncol Rep. 2006;16:497-503 pubmed
    ..was performed in lymphocytes by using PCR-RFLP (GSTA1, GSTP1), PCR (GSTT1, GSTM1) and sequencing analysis (UGT1A1 *28)...
  59. Martins R, Morais A, Dias A, Soares I, Rolão C, Ducla Soares J, et al. Early modification of sickle cell disease clinical course by UDP-glucuronosyltransferase 1A1 gene promoter polymorphism. J Hum Genet. 2008;53:524-8 pubmed publisher
    ..We investigated whether the (TA)n promoter polymorphism in the UDP-glucuronosyltransferase 1A1 gene (UGT1A1) may modify bilirubin metabolism, influencing bilirubinaemia, predisposition to cholelithiasis and subsequent ..
  60. McLeod H, Sargent D, Marsh S, Green E, King C, Fuchs C, et al. Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial N9741. J Clin Oncol. 2010;28:3227-33 pubmed publisher
    ..Genotyping was performed using pyrosequencing. All variants were polymorphic. The homozygous UGT1A1*28 allele observed in 9% of patients was associated with risk of grade 4 neutropenia in patients on IROX (55% v 15%..
  61. Martinez Balibrea E, Manzano J, Martinez Cardus A, Moran T, Cirauqui B, Catot S, et al. Combined analysis of genetic polymorphisms in thymidylate synthase, uridine diphosphate glucoronosyltransferase and X-ray cross complementing factor 1 genes as a prognostic factor in advanced colorectal cancer patients treated with 5-fluorouracil plu. Oncol Rep. 2007;17:637-45 pubmed
    ..synthase (TS), X-ray cross complementing factor 1 (XRCC1) and uridine diphosphate glucoronosyltransferase (UGT1A1 *28) polymorphism genotypes in response rate and time to progression (TTP) in metastatic colorectal cancer ..
  62. Tsezou A, Tzetis M, Giannatou E, Spanos I, Roma E, Fretzayas A, et al. Gilbert syndrome as a predisposing factor for cholelithiasis risk in the Greek adult population. Genet Test Mol Biomarkers. 2009;13:143-6 pubmed publisher
    We investigated the hypothesis that coinheritance of the common A(TA)(n)TAA promoter mutation at the UGT1A1 locus associated with Gilbert syndrome is a risk factor for gallstone formation in a homogeneous adult population, by conducting a ..
  63. Rouits E, Charasson V, Petain A, Boisdron Celle M, Delord J, Fonck M, et al. Pharmacokinetic and pharmacogenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer patients. Br J Cancer. 2008;99:1239-45 pubmed publisher
    ..for metastatic colorectal cancer with a combination of 5-fluorouracil and irinotecan; a polymorphism in the UGT1A1 gene (TA repeat in the TATA box) and one in the CES2 gene promoter (830C>G) were studied as potential markers ..
  64. Rantner B, Kollerits B, Anderwald Stadler M, Klein Weigel P, Gruber I, Gehringer A, et al. Association between the UGT1A1 TA-repeat polymorphism and bilirubin concentration in patients with intermittent claudication: results from the CAVASIC study. Clin Chem. 2008;54:851-7 pubmed publisher
    ..are strongly correlated with the enzyme activity of the hepatic uridine diphosphate glucuronosyltransferase (UGT1A1)...
  65. Hazama S, Mishima H, Tsunedomi R, Okuyama Y, Kato T, Takahashi K, et al. UGT1A1*6, 1A7*3, and 1A9*22 genotypes predict severe neutropenia in FOLFIRI-treated metastatic colorectal cancer in two prospective studies in Japan. Cancer Sci. 2013;104:1662-9 pubmed publisher
    ..A total of 73 patients agreed to additional analysis, and were genotyped for UGT1A polymorphisms, UGT1A1*28 (TA6>TA7), UGT1A1*6 (211G>A), UGT1A1*27 (686C>A), UGT1A1*60 (-3279T>G), UGT1A1*93 (-3156G>A), ..
  66. Petit F, Gajdos V, Capel L, Parisot F, Myara A, Francoual J, et al. Crigler-Najjar type II syndrome may result from several types and combinations of mutations in the UGT1A1 gene. Clin Genet. 2006;69:525-7 pubmed
  67. Operaña T, Tukey R. Oligomerization of the UDP-glucuronosyltransferase 1A proteins: homo- and heterodimerization analysis by fluorescence resonance energy transfer and co-immunoprecipitation. J Biol Chem. 2007;282:4821-9 pubmed
    ..This technique demonstrated that UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 self-oligomerize (homodimerize)...
  68. Hoskins J, Goldberg R, Qu P, Ibrahim J, McLeod H. UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. J Natl Cancer Inst. 2007;99:1290-5 pubmed
    The Food and Drug Administration and Pfizer changed the package insert for irinotecan to include a patient's UGT1A1*28 genotype as a risk factor for severe neutropenia on the basis of the findings of four pharmacogenetic studies, which ..
  69. Lara P, Natale R, Crowley J, Lenz H, Redman M, Carleton J, et al. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009;27:2530-5 pubmed publisher
    ..PG analysis showed that ABCB1 (C3435T)T/T (membrane transport) was associated with IP-related diarrhea; UGT1A1 (G-3156A)A/A (drug metabolism) was associated with IP-related neutropenia...
  70. Kaplan M, Renbaum P, Vreman H, Wong R, Levy Lahad E, Hammerman C, et al. (TA)n UGT 1A1 promoter polymorphism: a crucial factor in the pathophysiology of jaundice in G-6-PD deficient neonates. Pediatr Res. 2007;61:727-31 pubmed
    ..reported in glucose-6-phosphate dehydrogenase (G-6-PD)-normal neonates who were also homozygous for (TA)7/(TA)7 (UGT1A1*28) uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT) promoter polymorphism (Gilbert syndrome)...
  71. Hong A, Huo D, Kim H, Niu Q, Fackenthal D, Cummings S, et al. UDP-Glucuronosyltransferase 1A1 gene polymorphisms and total bilirubin levels in an ethnically diverse cohort of women. Drug Metab Dispos. 2007;35:1254-61 pubmed
    The objective of this study was to investigate variations in UGT1A1 polymorphisms and haplotypes among African-American and Caucasian women and to assess whether variants other than UGT1A1*28 are associated with total serum bilirubin ..
  72. Dai X, Wu C, He Y, Gui L, Zhou L, Guo H, et al. A genome-wide association study for serum bilirubin levels and gene-environment interaction in a Chinese population. Genet Epidemiol. 2013;37:293-300 pubmed publisher
    ..Gene-environment interactions were further examined. Briefly, two previously reported loci, UGT1A1 on 2q37 (rs6742078 and rs4148323, combined P = 1.44 × 10(-89) and P = 5...
  73. Dura P, Salomon J, Te Morsche R, Roelofs H, Kristinsson J, Wobbes T, et al. High enzyme activity UGT1A1 or low activity UGT1A8 and UGT2B4 genotypes increase esophageal cancer risk. Int J Oncol. 2012;40:1789-96 pubmed publisher
    ..Predicted enzyme activity groups were combined and compared between patients and controls. The UGT1A1 and UGT1A8 predicted high enzyme activity genotypes were significantly more (OR=1.62; 95% CI, 1.02-2...
  74. Rodrigues C, Vieira E, Santos R, de Carvalho J, Santos Silva A, Costa E, et al. Impact of UGT1A1 gene variants on total bilirubin levels in Gilbert syndrome patients and in healthy subjects. Blood Cells Mol Dis. 2012;48:166-72 pubmed publisher
    The Gilbert syndrome is a benign form of unconjugated hyperbilirubinemia, mainly associated with alterations in UGT1A1 gene...
  75. Hu Z, Yu Q, Zhao Y. Dose-dependent association between UGT1A1*28 polymorphism and irinotecan-induced diarrhoea: a meta-analysis. Eur J Cancer. 2010;46:1856-65 pubmed publisher
    ..The associations between the UGT1A1*28 polymorphism and irinotecan-induced diarrhoea remains controversial because of conflicting data in the ..
  76. Araki K, Fujita K, Ando Y, Nagashima F, Yamamoto W, Endo H, et al. Pharmacogenetic impact of polymorphisms in the coding region of the UGT1A1 gene on SN-38 glucuronidation in Japanese patients with cancer. Cancer Sci. 2006;97:1255-9 pubmed
    Pharmacogenetic testing for UDP-glucuronosyltransferase (UGT) 1A1*28, a promoter variant of the UGT1A1 gene, is now carried out clinically to estimate the risk of irinotecan-associated toxicity...
  77. Hu Z, Yu Q, Pei Q, Guo C. Dose-dependent association between UGT1A1*28 genotype and irinotecan-induced neutropenia: low doses also increase risk. Clin Cancer Res. 2010;16:3832-42 pubmed publisher
    A previous meta-analysis showed that the association between the UGT1A1*28 genotype and irinotecan-induced neutropenia was influenced by irinotecan dose and that the risk of neutropenia was similar at low doses for patients with all ..
  78. Zhang A, Xing Q, Qin S, Du J, Wang L, Yu L, et al. Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations. Pharmacogenomics J. 2007;7:333-8 pubmed
    Variants within the human UGT1A1 gene are associated with irinotecan induced severely adverse reactions and hyperbilirubinemia...
  79. Ruzzo A, Graziano F, Loupakis F, Santini D, Catalano V, Bisonni R, et al. Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy. Pharmacogenomics J. 2008;8:278-88 pubmed
    ..Risk for Grade III-IV neutropenia was significantly associated with UGT1A1*28 7/7 genotype...
  80. Liu C, Chen P, Chiou T, Liu J, Lin J, Lin T, et al. UGT1A1*28 polymorphism predicts irinotecan-induced severe toxicities without affecting treatment outcome and survival in patients with metastatic colorectal carcinoma. Cancer. 2008;112:1932-40 pubmed publisher
    It is known that the uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1)*28 polymorphism reduces UGT1A1 enzyme activity, which may lead to severe toxicities in patients who receive irinotecan...
  81. Lingenhel A, Kollerits B, Schwaiger J, Hunt S, Gress R, Hopkins P, et al. Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease. Exp Gerontol. 2008;43:1102-7 pubmed publisher
    ..b>UGT1A1 is the major gene influencing bilirubin concentrations...
  82. Chen G, Ramos E, Adeyemo A, Shriner D, Zhou J, Doumatey A, et al. UGT1A1 is a major locus influencing bilirubin levels in African Americans. Eur J Hum Genet. 2012;20:463-8 pubmed publisher
    ..Thirty-nine SNPs spanning a 78?kb region within the UGT1A1 displayed P-values <5 × 10(-8). The lowest P-value was 1.7 × 10(-22) for SNP rs887829...
  83. Sato H, Uchida T, Toyota K, Kanno M, Hashimoto T, Watanabe M, et al. Association of breast-fed neonatal hyperbilirubinemia with UGT1A1 polymorphisms: 211G>A (G71R) mutation becomes a risk factor under inadequate feeding. J Hum Genet. 2013;58:7-10 pubmed publisher
    ..We previously reported that 211G>A (G71R) mutation of the UGT1A1 gene is prevalent in East Asians and is associated with the development of neonatal hyperbilirubinemia...
  84. Watchko J, Lin Z, Clark R, Kelleher A, Walker M, Spitzer A. Complex multifactorial nature of significant hyperbilirubinemia in neonates. Pediatrics. 2009;124:e868-77 pubmed publisher
    To determine whether glucose-6-phosphate dehydrogenase (G6PD), uridine-diphosphoglucuronosyltransferase 1A1 (UGT1A1), and hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) gene variants occur at greater frequency in neonates ..
  85. Fakih M, Ross M, Starostik P. Increased frequency of uridine diphosphate glucuronosyltransferase 1A1 7/7 in patients experiencing severe irinotecan-induced toxicities. Clin Colorectal Cancer. 2007;6:583-7 pubmed
    ..We evaluated UGT1A1 polymorphism in patients developing grade 3/4 toxicity after initiation of irinotecan to determine the frequency ..
  86. Levesque E, Girard H, Journault K, Lepine J, Guillemette C. Regulation of the UGT1A1 bilirubin-conjugating pathway: role of a new splicing event at the UGT1A locus. Hepatology. 2007;45:128-38 pubmed
    UDP-glucuronosyltransferase 1A1 (UGT1A1) is involved in a wide range of biological and pharmacological processes because of its critical role in the conjugation of a diverse array of endogenous and exogenous compounds...
  87. D Silva S, Colah R, Ghosh K, Mukherjee M. UDP-glucuronosyltransferase 1A1 (UGT1A1) gene haplotypes and their effect on serum bilirubin concentration in healthy Indian adults. Gene. 2013;513:36-9 pubmed publisher
    ..study was to investigate the allele and genotype frequencies and haplotype structures of the variants in the UGT1A1 gene and their association with serum bilirubin levels in healthy adults...
  88. Hanchard N, Skierka J, Weaver A, Karon B, Matern D, Cook W, et al. UGT1A1 sequence variants and bilirubin levels in early postnatal life: a quantitative approach. BMC Med Genet. 2011;12:57 pubmed publisher
    ..Previous genetic studies have focused on the UGT1A1 gene, associating common variation in the coding or promoter regions with qualitative assessments of bilirubin (i...
  89. Sun G, Wu M, Cao J, Du L. Cord blood bilirubin level in relation to bilirubin UDP-glucuronosyltransferase gene missense allele in Chinese neonates. Acta Paediatr. 2007;96:1622-5 pubmed
    To investigate bilirubin UDP-glucuronosyltransferase (UGT1A1) gene allele in healthy Chinese neonates, their cord bilirubin level and the subsequent hyperbilirubinemia to determine relationships among them...
  90. Jylhävä J, Lyytikäinen L, Kahonen M, Hutri Kähönen N, Kettunen J, Viikari J, et al. A genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study. PLoS ONE. 2012;7:e35426 pubmed publisher
    ..1 (UGT1) family locus, and the most significant SNPs localised within the UGT1 polypeptide A1 (UGT1A1) gene region...
  91. Ferraldeschi R, Minchell L, Roberts S, Tobi S, Hadfield K, Blackhall F, et al. UGT1A1*28 genotype predicts gastrointestinal toxicity in patients treated with intermediate-dose irinotecan. Pharmacogenomics. 2009;10:733-9 pubmed publisher
    Variants in UGT1A1 have previously been associated with toxicity from irinotecan chemotherapy...