title: Genetic variant in the BCL11A (rs1427407), but not HBS1-MYB (rs6934903) loci associate with fetal hemoglobin levels in Indian sickle cell disease patients.
abstract: India along with Nigeria and DRC contribute to 57% of the world sickle cell anemia population. The annual number of newborns in India with SCA was estimated at 44,000 in 2010. Even with this high prevalence there is minimal information about genetic factors that influence the disease course in Indian patients. The current study was conducted on 240 patients with SCD and 60 with sickle cell trait, to determine the association of genetic variants at the BCL11A (rs1427407) and HBS1-MYB (rs6934903) loci with fetal hemoglobin levels (HbF). Both these loci have been implicated with influencing HbF levels, a powerful modulator of the clinical and hematologic features of SCD. Our results indicate the BCL11A rs1427407 G>T variant to be significantly associated with HbF levels {19.12±6.61 (GG), 20.27±6.92 (GT) and 24.83±2.92 (TT) respectively} contributing to ~23% of the trait variance. Interestingly no association of the HBS1L-MYB rs6934903 with the HbF levels was seen. The present study indicates the BCL11A (rs1427407) but not HMIP (rs6934903) to be associated with elevated HbF levels in Indian patient. Further interrogation of additional variants at both the loci; as also a GWAS which may help uncover new loci controlling HbF levels.
authors.affiliation: Research and Development, SRL Ltd, Prime Square Building, Plot No 1, S. V. Road, Goregaon (W), Mumbai 400 062, India. Electronic address: aparna.bhanushali@srl.in.
authors.forename: Aparna A
authors.initials: AA
authors.lastname: Bhanushali
authors.affiliation: Department of Biochemistry, Pt. J.N.M. Medical College, Raipur (C. G.), India. Electronic address: pkp1964@yahoo.co.in.
authors.forename: P K
authors.initials: PK
authors.lastname: Patra
authors.affiliation: Research and Development, SRL Ltd, Prime Square Building, Plot No 1, S. V. Road, Goregaon (W), Mumbai 400 062, India. Electronic address: devika.nair04@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Nair
authors.affiliation: Department of Biochemistry, Pt. J.N.M. Medical College, Raipur (C. G.), India. Electronic address: henu.verma@yahoo.com.
authors.forename: H
authors.initials: H
authors.lastname: Verma
authors.affiliation: Research and Development, SRL Ltd, Prime Square Building, Plot No 1, S. V. Road, Goregaon (W), Mumbai 400 062, India. Electronic address: brdas@srl.in.
authors.forename: B R
authors.initials: BR
authors.lastname: Das
mesh_terms: D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism*; D014644:Genetic Variation; D006801:Humans; D007194:India; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D020626:Oncogene Proteins v-myb / Q000235:genetics*; D012097:Repressor Proteins; D012805:Sickle Cell Trait / Q000097:blood / Q000235:genetics
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D020626:Oncogene Proteins v-myb; D012097:Repressor Proteins; C516308:SETA binding protein 1, human; D005319:Fetal Hemoglobin
keywords: BCL11A; Fetal hemoglobin; HBS1-MYB; India; Sickle cell Disease