Genomes and Genes
Summary: Structural proteins of the alpha-lipoproteins (HIGH DENSITY LIPOPROTEINS), including APOLIPOPROTEIN A-I and APOLIPOPROTEIN A-II. They can modulate the activity of LECITHIN CHOLESTEROL ACYLTRANSFERASE. These apolipoproteins are low in atherosclerotic patients. They are either absent or present in extremely low plasma concentration in TANGIER DISEASE.
- Hahne P, Krempler F, Schaap F, Soyal S, Höffinger H, Miller K, et al. Determinants of plasma apolipoprotein A-V and APOA5 gene transcripts in humans. J Intern Med. 2008;264:452-62 pubmed publisher..Associations of APOA5 transcripts with PPARA and CPT1A1 transcripts suggest that APOA5 expression is intimately linked to hepatic lipid metabolism. ..
- Sousa M, Alia P, Pintó X, Corbella E, Navarro M. Interaction between APOA5 -1131T>C and APOE polymorphisms and their association with severe hypertriglyceridemia. Clin Chim Acta. 2008;395:68-71 pubmed publisher..4 (95%CI:2.28-18.01). These data provide evidence that APOA5 -1131T>C polymorphism is associated with risk for severe HTG. Furthermore, this effect is strongly increased when -1131C variant is combined with APOE variants. ..
- Chien K, Fang W, Wen H, Lin H, Lin Y, Lin S, et al. APOA1/C3/A5 haplotype and risk of hypertriglyceridemia in Taiwanese. Clin Chim Acta. 2008;390:56-62 pubmed publisher..553TT had a 116% higher triglyceride concentration compared with those carrying common allele. The APOA1/C3/A5 haplotype represents an important locus for predicting risk of hypertriglyceridemia among Taiwanese. ..
- Wang J, Ban M, Kennedy B, Anand S, Yusuf S, Huff M, et al. APOA5 genetic variants are markers for classic hyperlipoproteinemia phenotypes and hypertriglyceridemia. Nat Clin Pract Cardiovasc Med. 2008;5:730-7 pubmed publisher..These two variants are robust genetic biomarkers of a range of clinical hyperlipoproteinemia phenotypes linked by hypertriglyceridemia. ..
- Liu Z, Hu M, Baum L, Thomas G, Tomlinson B. Associations of polymorphisms in the apolipoprotein A1/C3/A4/A5 gene cluster with familial combined hyperlipidaemia in Hong Kong Chinese. Atherosclerosis. 2010;208:427-32 pubmed publisher..Some common polymorphisms and haplotypes in APOA5 are closely associated with FCH in Hong Kong Chinese, and these differ from those found in Caucasians. ..
- Jang Y, Chae J, Kim O, Park H, Kim J, Paik J, et al. APOA5-1131T>C genotype effects on apolipoprotein A5 and triglyceride levels in response to dietary intervention and regular exercise (DIRE) in hypertriglyceridemic subjects. Atherosclerosis. 2010;211:512-9 pubmed publisher..APOA5-1131T/T carriers may benefit more from the DIRE than C allele carriers. These effects were remarkable in patients with moderate hypertriglyceridemia and the individuals with good compliance. ..
- Hubacek J, Bohuslavova R, Skodova Z, Pitha J, Bobkova D, Poledne R. Polymorphisms in the APOA1/C3/A4/A5 gene cluster and cholesterol responsiveness to dietary change. Clin Chem Lab Med. 2007;45:316-20 pubmed..s.). Other variants analyzed did not influence the change in lipid measurements over time. APOA4 and APOA5 variants may play an important role in the individual sensitivity of lipid parameters to dietary composition in men. ..
- Hallman D, Srinivasan S, Chen W, Boerwinkle E, Berenson G. Longitudinal analysis of haplotypes and polymorphisms of the APOA5 and APOC3 genes associated with variation in serum triglyceride levels: the Bogalusa Heart Study. Metabolism. 2006;55:1574-81 pubmed..However, the degree to which polymorphisms in the APOC3 and APOA5 genes may be independently associated with triglyceride levels remains to be determined. ..
- Shu X, Nelbach L, Weinstein M, Burgess B, Beckstead J, Young S, et al. Intravenous injection of apolipoprotein A-V reconstituted high-density lipoprotein decreases hypertriglyceridemia in apoav-/- mice and requires glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1. Arterioscler Thromb Vasc Biol. 2010;30:2504-9 pubmed publisher..Its intravenous administration may have therapeutic benefit in human subjects with severe HTG, especially in cases involving apoA-V variants associated with HTG. ..
- Zhao S, Hu S, Li J, Hu M, Liu Q, Wu L, et al. Association of human serum apolipoprotein A5 with lipid profiles affected by gender. Clin Chim Acta. 2007;376:68-71 pubmed..198, P=0.167 for male). The serum concentration of ApoA5 was very low. The concentration of ApoA5 was negatively correlated with TG and BMI, but positively correlated with HDL-C. The correlations were affected by gender. ..
- Dallongeville J, Cottel D, Wagner A, Ducimetiere P, Ruidavets J, Arveiler D, et al. The APOA5 Trp19 allele is associated with metabolic syndrome via its association with plasma triglycerides. BMC Med Genet. 2008;9:84 pubmed publisher..The APOA5 Trp19 allele increased susceptibility to metabolic syndrome via its impact on plasma triglyceride levels. ..
- Li X, Xu Y, Ding Y, Qin C, Dai Z, Niu L. Polymorphism of apolipoprotein A5 is a risk factor for cerebral infarction in type 2 diabetes. J Huazhong Univ Sci Technolog Med Sci. 2008;28:653-6 pubmed publisher..It was concluded that the apoA5 -1131C allele variant is an independent genetic risk factor for T2DMCI. ..
- Maasz A, Kisfali P, Jaromi L, Horvatovich K, Szolnoki Z, Csongei V, et al. Apolipoprotein A5 gene IVS3+G476A allelic variant confers susceptibility for development of ischemic stroke. Circ J. 2008;72:1065-70 pubmed..All of the 3 APOA5 variants are associated with elevated triglycerides, but only the -1131C and the IVS3+476A alleles confer risk for all types of ischemic stroke; such an association could not be detected for the 1259C allele. ..
- Johansen C, Wang J, Lanktree M, Cao H, McIntyre A, Ban M, et al. Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nat Genet. 2010;42:684-7 pubmed publisher..1% of affected individuals and 15.3% of controls (P = 2.6 x 10(-5)). Considering rare variants in these genes incrementally increased the proportion of genetic variation contributing to HTG. ..
- Palmen J, Smith A, Dorfmeister B, Putt W, Humphries S, Talmud P. The functional interaction on in vitro gene expression of APOA5 SNPs, defining haplotype APOA52, and their paradoxical association with plasma triglyceride but not plasma apoAV levels. Biochim Biophys Acta. 2008;1782:447-52 pubmed publisher..We conclude that APOA5 expression, and not circulating plasma apoAV levels, is causatively associated with plasma TG levels. ..
- Dichlberger A, Cogburn L, Nimpf J, Schneider W. Avian apolipoprotein A-V binds to LDL receptor gene family members. J Lipid Res. 2007;48:1451-6 pubmed..We propose that a direct interaction with LRs may represent a novel, additional mechanism for the modulation of TG levels by apoA-V. ..
- Havasi V, Szolnoki Z, Talian G, Bene J, Komlosi K, Maasz A, et al. Apolipoprotein A5 gene promoter region T-1131C polymorphism associates with elevated circulating triglyceride levels and confers susceptibility for development of ischemic stroke. J Mol Neurosci. 2006;29:177-83 pubmed..Being that apoA5 gene is under the control of the peroxisome proliferator-activated receptor alpha, theoretically, the current observations also can have long-term therapeutic consequences. ..
- Sarwar N, Sandhu M, Ricketts S, Butterworth A, Di Angelantonio E, Boekholdt S, et al. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010;375:1634-9 pubmed publisher..These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease. British Heart Foundation, UK Medical Research Council, Novartis. ..
- Jiang C, Liu B, Cheung B, Lam T, Lin J, Li Jin Y, et al. A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese. Eur J Hum Genet. 2010;18:1255-60 pubmed publisher..The corroborative findings in two independent populations indicate that the APOA5-1131T>C polymorphism is an important and clinically relevant determinant of plasma triglyceride levels in the Chinese population. ..
- Talmud P, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, et al. Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. Am J Hum Genet. 2009;85:628-42 pubmed publisher..These genes provide further insights into lipid metabolism and the likely effects of modifying the encoded targets therapeutically. ..
- Hubacek J, Adamkova V, Prusikova M, Snejdrlova M, Hirschfeldova K, Lanska V, et al. Impact of apolipoprotein A5 variants on statin treatment efficacy. Pharmacogenomics. 2009;10:945-50 pubmed publisher..9 +/- 12.5%; p < 0.005, Mann-Whitney test). This result was independent of sex, age, BMI and APOE polymorphism. Our results suggest that the APOA5 gene variants may play an important role in the pharmacogenetics of statin treatment. ..
- Wang J, Cao H, Ban M, Kennedy B, Zhu S, Anand S, et al. Resequencing genomic DNA of patients with severe hypertriglyceridemia (MIM 144650). Arterioscler Thromb Vasc Biol. 2007;27:2450-5 pubmed..The findings underscore the value of candidate gene resequencing to understand the genetic contribution in complex lipoprotein and metabolic disorders. ..
- Yamada Y, Ichihara S, Kato K, Yoshida T, Yokoi K, Matsuo H, et al. Genetic risk for metabolic syndrome: examination of candidate gene polymorphisms related to lipid metabolism in Japanese people. J Med Genet. 2008;45:22-8 pubmed..APOA5, LDLR, CYP3A4 and C1QTNF5 are susceptibility loci for metabolic syndrome in Japanese people. Genotypes for these polymorphisms may prove informative for prediction of genetic risk for metabolic syndrome. ..
- Grallert H, Sedlmeier E, Huth C, Kolz M, Heid I, Meisinger C, et al. APOA5 variants and metabolic syndrome in Caucasians. J Lipid Res. 2007;48:2614-21 pubmed..Furthermore, the data suggest a different mechanism of APOA5 impact on MetS in Caucasians, as variant c.56C>G (not analyzed in the Japanese study) and not -1131T>C, as in the Japanese subjects, was associated with MetS. ..
- Chien K, Chen M, Hsu H, Su T, Chang W, Lee C, et al. Genetic association study of APOA1/C3/A4/A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population. Clin Chim Acta. 2008;388:78-83 pubmed..001). There is an important role of APOA1/C3/A4/A5 gene polymorphisms and haplotypes in the development of high triglyceride/HDL ratio in Chinese. ..
- Evans D, Aberle J, Beil F. Resequencing the apolipoprotein A5 (APOA5) gene in patients with various forms of hypertriglyceridemia. Atherosclerosis. 2011;219:715-20 pubmed publisher..Rare mutations in the APOA5 gene are more frequent in patients with elevated triglycerides than in those with Type III HLP. ..
- Maasz A, Kisfali P, Szolnoki Z, Hadarits F, Melegh B. Apolipoprotein A5 gene C56G variant confers risk for the development of large-vessel associated ischemic stroke. J Neurol. 2008;255:649-54 pubmed publisher..Thereby, the 56G allele differs from the APOA5 T-1131C allelic variant, which has been previously identified as a risk factor for all subgroups of the stroke disease. ..
- Henneman P, Schaap F, Rensen P, van Dijk K, Smelt A. Estrogen induced hypertriglyceridemia in an apolipoprotein AV deficient patient. J Intern Med. 2008;263:107-8 pubmed
- Ken Dror G, Goldbourt U, Dankner R. Different effects of apolipoprotein A5 SNPs and haplotypes on triglyceride concentration in three ethnic origins. J Hum Genet. 2010;55:300-7 pubmed publisher..These results suggest that different SNPs in ApoA5 polymorphisms may be associated with triglyceride concentration and CVD in each of these ethnic origins. ..
- Song K. Orphan nuclear receptor Nur77 participates in human apolipoprotein A5 gene expression. Biochem Biophys Res Commun. 2010;392:63-6 pubmed publisher..Taken together, our results demonstrated that Nur77 is a novel regulator of human ApoA5 gene expression and provide a new insight into the role of this orphan nuclear receptor in lipoprotein metabolism and triglyceride homeostasis. ..
- Olano Martin E, Abraham E, Gill Garrison R, Valdes A, Grimaldi K, Tang F, et al. Influence of apoA-V gene variants on postprandial triglyceride metabolism: impact of gender. J Lipid Res. 2008;49:945-53 pubmed publisher..015). However, in linear regression analysis, a significant independent association with TG AUC (P = 0.007) was only evident for the apoA-V -1131 T>C SNP, indicating a greater relative importance of the apoA-V genotype. ..
- Shen L, Pearson K, Xiong Y, Lo C, Tso P, Woods S, et al. Characterization of apolipoprotein A-IV in brain areas involved in energy homeostasis. Physiol Behav. 2008;95:161-7 pubmed publisher..These data collectively support the hypothesis that apo A-IV, produced by neuronal cells, may exert its anorectic action by interacting with catabolic regulatory neuropeptides. ..
- Matsunaga A, Arishima H, Niimura H, Zhang B, Uehara Y, Ohwaki K, et al. Strong linkage disequilibrium and association of -1131T>C and c.553G>T polymorphisms of the apolipoprotein A5 gene with hypertriglyceridemia in a Japanese population. Circ J. 2007;71:746-52 pubmed..The -1131T>C and c.553G>T (G185C) polymorphisms correlated with HTG in this Japanese population, but neither polymorphism directly affected ApoA5 expression. ..
- Kisfali P, Mohas M, Maasz A, Polgar N, Hadarits F, Marko L, et al. Haplotype analysis of the apolipoprotein A5 gene in patients with the metabolic syndrome. Nutr Metab Cardiovasc Dis. 2010;20:505-11 pubmed publisher..In addition, as our current data suggest, the novel APOA5*5 haplotype can confer protection against MS. ..
- Hubacek J, Lanska V, Skodova Z, Adamkova V, Poledne R. Sex-specific interaction between APOE and APOA5 variants and determination of plasma lipid levels. Eur J Hum Genet. 2008;16:135-8 pubmed..05) mmol/l) than others (1.37 (0.75) mmol/l) (P<0.01). In male subjects, the same, but non-significant trend was observed. In female subjects, we have detected an interaction between APOE and APOA5 variants and plasma lipid levels. ..
- Yu Y, Xue L, Zhao C. [Study on polymorphism in the apolipoprotein A5 gene in patients with premature coronary heart disease]. Beijing Da Xue Xue Bao Yi Xue Ban. 2007;39:576-80 pubmed..The APOA5-1131T/C polymorphism has influence on serum TG level, and the APOA5-1131C allele is associated with the development of premature coronary heart disease in northern Chinese Han population. ..
- Ong K, Jiang C, Liu B, Jin Y, Tso A, Tam S, et al. Association of a genetic variant in the apolipoprotein A5 gene with the metabolic syndrome in Chinese. Clin Endocrinol (Oxf). 2011;74:206-13 pubmed publisher..Our results showed that the -1131T>C polymorphism in APOA5 was associated with the MetS because of its strong effect on plasma triglycerides. This may partly explain the higher cardiovascular risk in people with this polymorphism. ..
- Ramakrishnan L, Sachdev H, Sharma M, Abraham R, Prakash S, Gupta D, et al. Relationship of APOA5, PPAR? and HL gene variants with serial changes in childhood body mass index and coronary artery disease risk factors in young adulthood. Lipids Health Dis. 2011;10:68 pubmed publisher..None of the polymorphisms had any significant relationship with birth weight or serial changes in anthropometry from birth to adulthood in this cohort. ..
- Dorfmeister B, Zeng W, Dichlberger A, Nilsson S, Schaap F, Hubacek J, et al. Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding. Arterioscler Thromb Vasc Biol. 2008;28:1866-71 pubmed publisher..Their occurrence in the homozygous state, coinheritance of LPL variants or common APOA5 TG-raising variant in trans, appears to be essential for their phenotypic expression. ..
- Yi Z, Cho S, Zhao H, Wu Y, Luo J, Li D, et al. A novel peptide from human apolipoprotein(a) inhibits angiogenesis and tumor growth by targeting c-Src phosphorylation in VEGF-induced human umbilical endothelial cells. Int J Cancer. 2009;124:843-52 pubmed publisher..Together, these studies provide the first evidence that KV11 from apolipoprotein KV domain has anti-angiogenesis functions and may be an anti-tumor drug candidate. ..
- Vasilopoulos Y, Sarafidou T, Bagiatis V, Skriapa L, Goutzelas Y, Pervanidou P, et al. Association between polymorphisms in MTHFR and APOA5 and metabolic syndrome in the Greek population. Genet Test Mol Biomarkers. 2011;15:613-7 pubmed publisher..001 and p=0.003, respectively), compared with noncarriers. These results support a role for MTHFR and APOA5 as risk factors for MetS and suggest their further validation in larger independent populations. ..
- Huang Y, Lin Y, Chiang C, Yen C, Lin S, Kao J. Functional importance of apolipoprotein A5 185G in the activation of lipoprotein lipase. Clin Chim Acta. 2012;413:246-50 pubmed publisher..APOA5 residue 185G is very important in LPL-mediated VLDL hydrolysis, and any mutation at this residue will decrease LPL activation and concomitant TG modulation. ..
- Nieminen T, Kahonen M, Islam S, Raitakari O, Hutri Kähönen N, Marniemi J, et al. Apolipoprotein A-I/C-III/A-IV SstI and apolipoprotein B XbaI polymorphisms do not affect early functional and structural changes in atherosclerosis: the Cardiovascular Risk in Young Finns study. Circ J. 2007;71:741-5 pubmed..The polymorphisms apoA-I/C-III/A-IV SstI and apoB XbaI do not seem to affect carotid artery characteristics or brachial artery FMD in young adulthood. ..
- Shah A, Rader D, Millar J. The effect of PPAR-alpha agonism on apolipoprotein metabolism in humans. Atherosclerosis. 2010;210:35-40 pubmed publisher..However, the benefit of the enhanced turnover of HDL apoA-I in response to PPAR-alpha activation remains to be determined. ..
- Mattei J, Demissie S, Tucker K, Ordovas J. Apolipoprotein A5 polymorphisms interact with total dietary fat intake in association with markers of metabolic syndrome in Puerto Rican older adults. J Nutr. 2009;139:2301-8 pubmed publisher..Dietary fat intake seems to modulate these associations. The results contribute to the understanding of health disparities in this population. ..
- Jang Y, Paik J, Hyun Y, Chae J, Kim J, Choi J, et al. The apolipoprotein A5 -1131T>C promoter polymorphism in Koreans: association with plasma APOA5 and serum triglyceride concentrations, LDL particle size and coronary artery disease. Clin Chim Acta. 2009;402:83-7 pubmed publisher..The APOA5 -1131C allele is associated with reduced APOA5 concentration and with increased CAD risk. This is consistent with the observed association between the -1131C SNP, increased triglycerides as well as small LDL particle size. ..
- Baum L, Ng M, So W, Poon E, Wang Y, Lam V, et al. A case-control study of apoA5 -1131T-->C polymorphism that examines the role of triglyceride levels in diabetic nephropathy. J Diabetes Complications. 2007;21:158-63 pubmed..The strong association between TG level and DN may be due to a factor that is usually closely linked to TG level but that is not affected by the apoA5 polymorphism. ..
- Hegele R, Pollex R. Apolipoprotein A-V genetic variation and plasma lipoprotein response to fibrates. Arterioscler Thromb Vasc Biol. 2007;27:1224-7 pubmed
- Cho T, Jung Y, Koschinsky M. Apolipoprotein(a), through its strong lysine-binding site in KIV(10'), mediates increased endothelial cell contraction and permeability via a Rho/Rho kinase/MYPT1-dependent pathway. J Biol Chem. 2008;283:30503-12 pubmed publisher..Studies are ongoing to further dissect the molecular basis of these findings. ..
- Priore Oliva C, Carubbi F, Schaap F, Bertolini S, Calandra S. Hypertriglyceridaemia and low plasma HDL in a patient with apolipoprotein A-V deficiency due to a novel mutation in the APOA5 gene. J Intern Med. 2008;263:450-8 pubmed publisher..Loss of function mutations of APOA5 gene may be the cause of severe HTG in patients without mutations in LPL and APOC2 genes. ..