Genomes and Genes
Affiliation: Medical College of Georgia
- The methylene tetrahydrofolate reductase (C677T) mutation as a potential risk factor for avascular necrosis in sickle cell diseaseA Kutlar
Sickle Cell Center, Department of Medicine, Medical College of Georgia, Augusta 30912, USA
Hemoglobin 25:213-7. 2001..6% in patients with AVN and 12.9% in those without AVN (p = 0.006). These data suggest that the thermolabile MTHFR variant may be a contributing risk factor for AVN in some populations with sickle cell disease...
- Sickle cell disease: a multigenic perspective of a single gene disorderAbdullah Kutlar
Sickle Cell Center, Medical College of Georgia, Augusta, Georgia 30912 3680, USA
Hemoglobin 31:209-24. 2007..This brief review focuses on the recent advances in our understanding of the impact of non globin genetic modifiers on the phenotypic diversity of the disease...
- Sickle cell disease: a multigenic perspective of a single-gene disorderAbdullah Kutlar
Sickle Cell Center, Medical College of Georgia, Augusta, GA 30912, USA
Med Princ Pract 14:15-9. 2005..Mention is made of genetic polymorphisms that might predispose to stroke. The application of gene expression profiling to the study of SCD is very promising and some preliminary data are provided...
- Genome-wide association study of cardiac structure and systolic function in African Americans: the Candidate Gene Association Resource (CARe) studyErvin R Fox
Department of Medicine, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216, USA
Circ Cardiovasc Genet 6:37-46. 2013..Using data from 4 community-based cohorts of African Americans, we tested the association between genome-wide markers (single-nucleotide polymorphisms) and cardiac phenotypes in the Candidate-gene Association Resource study...
- A dose-escalation phase IIa study of 2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell diseaseAbdullah Kutlar
Adult Sickle Cell Center, Georgia Regents University Medical Center, Augusta, GA, USA
Am J Hematol 88:E255-60. 2013..Total hemoglobin increased by a mean of 0.65 g/dL (95% CI, 0.5-1.0 g/dL), and 13 subjects (25%) had increases ≥1 g/dL. Future studies are warranted to evaluate the therapeutic potential of HQK-1001 in sickle cell disease. ...
- Neonatal cyanosis due to a novel fetal hemoglobin: Hb F-Circleville [Ggamma63(E7)His-->Leu, CAT>CTT]Erin Dainer
Department of Medicine, Medical College of Georgia, Augusta, GA 30912, USA
Hemoglobin 32:596-600. 2008..Here we describe a novel fetal Hb variant, Hb F-Circleville [Ggamma63(E7)His-->Leu], associated with methemoglobinemia and cyanosis in the newborn. The patient's sister also had neonatal cyanosis at birth...
- Regular transfusion lowers plasma free hemoglobin in children with sickle-cell disease at risk for strokeNelson E Lezcano
Department of Neurology, School of Medicine, Medical College of Georgia, Augusta, GA 30912, USA
Stroke 37:1424-6. 2006..PFH has been associated with harmful endothelial actions including scavenging nitric oxide (NO). Whether PFH plays a role in stroke in SCD has not been examined...
- Hb Fulton-Georgia [α20(B1)His→Pro; HBA1: c.62A>C]: a new α-globin variant coinherited with α-thalassemia-2 (3.7 kb deletion) and Hb SC diseaseLina Zhuang
Department of Medicine, Georgia Health Sciences University Medical College of Georgia, Augusta, Georgia, USA
Hemoglobin 37:481-5. 2013..Coinheritance of Hb Fulton-Georgia, heterozygous α-thal-2 and Hb SC disease was associated with a mild phenotype, consisting of microcytosis and anisocytosis, but no anemia or other hematological abnormality. ..
- The proinflammatory cytokine GM-CSF downregulates fetal hemoglobin expression by attenuating the cAMP-dependent pathway in sickle cell diseaseTohru Ikuta
Department of Anesthesiology and Perioperative Medicine, Medical College of Georgia, Georgia Health Sciences University, Augusta, USA
Blood Cells Mol Dis 47:235-42. 2011..Reduction in GM-CSF levels upon hydroxyurea therapy may be critical for efficient HbF induction. The results showing the involvement of GM-CSF in HbF expression may suggest possible mechanisms for hydroxyurea resistance in SCD...
- Two new hemoglobin variants: Hb Tallahassee [α3(A1)Ser→Tyr; HBA2: c.11C>A] and Hb madison-NC [β119(GH2)Gly→Ser; HBB: c.358G>A]Ferdane Kutlar
Department of Medicine, Medical College of Georgia Georgia Regents University, Augusta, Georgia, USA
Hemoglobin 38:207-10. 2014..11C > A] named Hb Tallahassee and the other is a β-globin chain variant located at codon 119 [β119(GH2)Gly→Ser; HBB: c.358G > A] called Hb Madison-NC...
- Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell miceSteffen E Meiler
Department of Anesthesiology and Perioperative Medicine, Georgia Health Sciences University, Augusta, GA, USA
Blood 118:1109-12. 2011..Surprisingly, combinatory therapy with both drugs failed to mitigate hydroxyurea's myelotoxic effects and caused loss of HbF induction. These findings support further evaluation of pomalidomide as a novel therapy for SCD...
- Two new hemoglobin variants: Hb Sinai-Greenspring [beta34(B16)Val-->Ile, GTC > ATC] and Hb Sinai-Bel Air [beta53(D4)Ala-->Asp, GCT > GAT]Erin Dainer
Sickle Cell Center, Department of Medicine, Medical College of Georgia, Augusta, GA 30912, USA
Hemoglobin 32:588-91. 2008..The variants were characterized by cation exchange high performance liquid chromatography (HPLC), reversed phase HPLC, and sequencing of amplified beta-globin genes. Functional studies could not be performed at this time...
- A novel approach to rapid determination of betaS-globin haplotypes: sequencing of the Agamma-IVS-II regionAmy E Vinson
Sickle Cell Center, Department of Medicine Medical College of Georgia, Augusta, Georgia, USA
Hemoglobin 28:317-23. 2004..We provide an algorithm that allows rapid assignment of the four African haplotypes carrying the sickle mutation...
- Acute splenic complications and implications of splenectomy in hemoglobin SC diseaseKarthi Subbannan
Department of Medicine, Section of Hematology Oncology, Sickle Cell Center, Medical College of Georgia, Augusta, Georgia 30912, USA
Eur J Haematol 83:258-60. 2009..Although it appears to be safe regarding short-term complications of surgery, long-term adverse effects such as infections have to be evaluated cautiously...
- Vasoactive factors in sickle cell disease: in vitro evidence for endothelin-1-mediated vasoconstrictionSitki Ergul
Division of Hematology and Oncology, Medical University of South Carolina, Charleston, SC, USA
Am J Hematol 76:245-51. 2004....
- A new Aγ-globin chain variant: Hb F-Sykesville MD [Aγ113(G15)Val → Ile; HBG1: c.340G>A] detected in a Caucasian babyNiren Patel
Department of Medicine, Georgia Regent s University Augusta, Augusta, Georgia, USA
Hemoglobin 39:52-4. 2015..In this report we discuss the molecular characteristics and diagnostic criteria of a new (A)γ chain variant that was detected during newborn screening and named Hb F-Sykesville MD [(A)γ113(G15)Val → Ile; HBG1: c.340G>A]...
- A phase 1/2 trial of HQK-1001, an oral fetal globin inducer, in sickle cell diseaseAbdullah Kutlar
Department of Medicine, Sickle Cell Center, Medical College of Georgia, Augusta, GA, USA
Am J Hematol 87:1017-21. 2012..These findings of favorable PK profiles, tolerability, early rises in HbF, and total Hgb indicate that trials of longer duration appear warranted to more definitively evaluate the therapeutic potential of HQK-1001 in sickle cell disease...
- The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-upMartin H Steinberg
Department of Medicine, Boston University School of Medicine, Boston Medical Center, Massachusetts, USA
Am J Hematol 85:403-8. 2010..Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality...
- Rare occurrence of Hb Lepore-Baltimore in African Americans: molecular characteristics and variations of Hb LeporesSean M McKeown
Department of Medicine, Medical College of Georgia, Augusta, GA, USA
Ann Hematol 88:545-8. 2009..We have used state-of-the-art technology, combining protein- and DNA-based methods, in the analysis of the hybrid hemoglobin and discuss its molecular characteristics...
- Sickle cell disease: a multigenic perspective of a single gene disorderAbdullah Kutlar
Medical College of Georgia, Sickle Cell Center, Augusta, GA, USA
Hematology 10:92-9. 2005
- Coagulation activation in sickle cell trait: an exploratory studyChirag Amin
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA
Br J Haematol 171:638-46. 2015..Further studies in larger cohorts of subjects with sickle cell trait are needed to confirm the results of this preliminary investigation. ..
- Two new γ chain variants: Hb F-Augusta GA [(G)γ59(E3)Lys → Arg; HBG2: c.179A > G] and Hb F-Port Royal-II [(A)γ125(H3)Glu → Ala; HBG1: c.377A > C]Ferdane Kutlar
Department of Medicine, Georgia Regents University at Augusta, Augusta, Georgia, USA and
Hemoglobin 38:376-80. 2014..One is a new (G)γ-globin chain variant, Hb F-Augusta GA [(G)γ59(E3)Lys → Arg; HBG2: c.179A > G] and the other one is Hb F-Port Royal-II [(A)γ125(H3)Glu → Ala; HBG1: c.377A > C]...
- Erythrocyte sickling during exercise and thermal stressMichael F Bergeron
Department of Physical Therapy, Medical College of Georgia, Augusta, GA 30912 0800, USA
Clin J Sport Med 14:354-6. 2004..To examine effects of exercise in the heat and fluid intake on erythrocyte sickling and neutrophil activation in carriers of sickle cell trait (HbAS)...
- Mortality in sickle cell patients on hydroxyurea therapySule M Bakanay
Sickle Cell Center, Department of Medicine, Office of Biostatistics and Bioinformatics, Medical College of Georgia, Augusta 30912, USA
Blood 105:545-7. 2005..Sickle cell patients who die while on HU therapy may represent a subgroup of older patients, possibly with more severe disease and more severe organ damage. Such patients need early identification and prompt HU institution...
- Genetic risk factors for cerebrovascular disease in children with sickle cell disease: design of a case-control association study and genomewide screenGaye T Adams
Sickle Cell Center, Department of Medicine, Medical College of Georgia, Augusta, GA, USA
BMC Med Genet 4:6. 2003..The genetic factors leading to the development of a high TCD velocity (i.e. cerebrovascular disease) and ultimately to stroke are not well characterized...
- Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource studyErvin R Fox
Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
Hum Mol Genet 20:2273-84. 2011..More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity...
- Endothelin-1 contributes to the progression of renal injury in sickle cell disease via reactive oxygen speciesJ Brett Heimlich
1epartment of Physiology, Augusta University, Augusta, GA 30912, USA
Br J Pharmacol 173:386-95. 2016..The current study was designed to determine whether ET-1 acting via the ETA receptor contributes to renal injury in a mouse model of sickle cell disease...
- Cellular adhesion and the endothelium: P-selectinAbdullah Kutlar
Sickle Cell Center, Department of Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA
Hematol Oncol Clin North Am 28:323-39. 2014....
- Interaction of sickle cell trait with hereditary spherocytosis: splenic infarcts and sequestrationCelatettin Ustun
Department of Medicine, Section of Hematology Oncology, Medical College of Georgia, Augusta, GA 30912, USA
Acta Haematol 109:46-9. 2003..The interaction of HS and SCT leads to RBC dehydration with increased MCHC and intracellular Hb S concentration presumably favoring intrasplenic sickling and resultant splenic infarcts and sequestration as seen in this case...
- Concordant fetal hemoglobin response to hydroxyurea in siblings with sickle cell diseaseMartin H Steinberg
Boston University School of Medicine, Room 211, 88 E Newton Street, Boston, MA 02118, USA
Am J Hematol 72:121-6. 2003..Our results provide additional evidence that some elements that regulate HbF expression are linked to the beta-globin gene cluster...
- Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatmentMartin H Steinberg
Boston University School of Medicine, Center of Excellence in Sickle Cell Disease, Boston Medical Center, Boston, Mass 02118, USA
JAMA 289:1645-51. 2003..Hydroxyurea increases levels of fetal hemoglobin (HbF) and decreases morbidity from vaso-occlusive complications in patients with sickle cell anemia (SCA). High HbF levels reduce morbidity and mortality...
- Alpha Thalassemia is associated with decreased risk of abnormal transcranial Doppler ultrasonography in children with sickle cell anemiaLewis L Hsu
Emory University School of Medicine and Georgia Comprehensive Sickle Cell Center, Atlanta, Georgia 30303, USA
J Pediatr Hematol Oncol 25:622-8. 2003..The authors hypothesized that children with abnormal TCD are less likely to have alpha thalassemia-2, and an increased hemoglobin level accounts for this protective effect...
- Hb Setif [alpha94(G1)Asp --> Tyr (alpha2)] detected in a Turkish familyGuncag Dincol
Division of Hematology, Department of Internal Medicine, Istanbul Medical School, University of Istanbul, Capa, Istanbul, Turkey
Hemoglobin 27:249-52. 2003
- Hemoglobin binding to A beta and HBG2 SNP association suggest a role in Alzheimer's diseaseRodney T Perry
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294 0022, USA
Neurobiol Aging 29:185-93. 2008..010) and >65 years (p=0.013), and families not homozygous for the APOE4 allele (p=0.041). We hypothesize that Hb F may be less toxic than adult Hb in its interaction with A beta and may protect against the development of AD...
- Molecular characterization of Hb D-Ibadan [beta87(F3)Thr-->Lys] in combination with Hb S [beta6(A3)Glu-->Val] and with beta+-Thalassemia: report of two casesRupa Redding-Lallinger
Department of Pediatrics and Internal Medicine, University of North Carolina, Chapel Hill 27599 7220, USA
Hemoglobin 26:129-34. 2002....
- Longitudinal changes in ferritin during chronic transfusion: a report from the Stroke Prevention Trial in Sickle Cell Anemia (STOP)Beatrice Files
Children s Healthcare of Atlanta Scottish Rite, Atlanta, Georgia 30342, USA
J Pediatr Hematol Oncol 24:284-90. 2002..Iron overload, the inevitable result of chronic transfusion, is commonly monitored with serum ferritin concentration...
- Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemiaKenneth I Ataga
Division of Hematology Oncology, University of North Carolina at Chapel Hill, CB no 7305, 3009 Old Clinic Bldg, Chapel Hill, NC 27599 7305, USA
Blood 111:3991-7. 2008..This study is registered at http://clinicaltrials.gov as NCT00040677...