Genetics of fetal hemoglobin in tribal Indian patients with sickle cell anemia


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Abstract

India tops the list of countries with sickle cell disease (SCD) with an estimated 44,000 live births in 2010 and a prevalence of 10%–33%. In the present study, the first from India, we have investigated the effect of genetic variants in theBCL11A, theHMIP(HBS1L-MYBintergenic polymorphism) locus, in addition to theHBBlocus, which are known to be associated with fetal hemoglobin (HbF) levels, a major modulator of the disease phenotype. The present study was conducted on 240 individuals with SCD and 60 with sickle cell trait. Genotyping was performed for theBCL11Ars11886868 and rs34211119;HMIPrs9399137, rs189600565, rs7776196, rs34778774, and rs53293029;HBG2Xmn1 polymorphism rs7482144; and −68C > THBDpromoter polymorphism. All the 3 quantitative trait loci were associated with HbF levels in Indian patients with SCD. The highest difference was seen in the Xmn1 single-nucleotide polymorphism, which accounted for 11% of the trait variance, theBCL11Ars11886868 for 3.65%, whereas theHMIPrs9399137 for 3.8%. The present study indicates theBCL11A,HMIP, and β-globin region to be associated with increased HbF levels in Indian patient. Further interrogation of these genotypes with respect to pain crisis is warranted in this population, which may help in prognostication, as also a genome-wide association study, which may help uncover new loci controlling HbF levels.

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