Modulatory effect of single nucleotide polymorphism in Xmn1, BCL11A and HBS1L-MYB loci on fetal hemoglobin levels in ? thalassemia major and Intermedia patients

Abstract

Objective: This study was aimed to evaluate the influence of these genetic modifiers (HBB gene cluster: rs7482144; BCL11A: rs766432; HBS1L-MYB: rs9399137) on the HbF levels in Thalassemia major and thalassemia intermedia.
Methods: The cohort study comprised of 52 patients with ?-thalassemia Intermedia and 64 patients of thalassemia major, all diagnosed in laboratories of Punjab thalassemia prevention program Hb-F was quantified by HPLC (Variant ll- Biorad). Primary mutation analysis and SNPS were done by ARMS PCR. SPSS version 20 i used for data analysis applying multivariate regression analysis.
Results: The levels of Hb-F were primarily influenced by alleles of the HBG2, (rs7482144), and BCL11A (rs766432) gene but SNP of HBS1L-MYB (rs9399137) has no significant role. The rs7482144 SNP explained 8.3% of the variation in the Hb-F levels, while 5% of trait variation was explained by rs766432.
Conclusion: There is clear association between Hb-F level and SNPs in HBG2, (rs7482144), and BCL11A (rs766432) gene. This correlation is additive and seen both in thalassemia major and thalassemia Intermedia cohorts, more so in case of later.

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