Abstract
OBJECTIVES: This study investigated the associations of the rs4671393, rs1427407, and rs11886868 genetic variants of the BCL11A gene and the rs9399137 variant of the HBS1L-MYB gene with thalassemia in patients from the population of Punjab, Pakistan. METHODS: A cohort of 600 participants, comprising 300 patients with thalassemia and 300 age- and sex-matched healthy controls, was recruited from various hospitals in Punjab, Pakistan. DNA was extracted from whole blood samples from all participants. Specific DNA regions containing four genetic variants of interest were amplified with polymerase chain reaction. RESULTS: The genotypic frequencies of the rs4671393 SNP of BCL11A indicated that the heterozygous (AG) genotype of this SNP was significantly associated with a nearly two-fold increased thalassemia risk, with respect to the control group (OR = 1.77; 95% CI = 1.77-2.80; p = 0.01). Combining all genotypes into a joint model further confirmed their significant association with thalassemia risk. Similarly to the findings for rs4671393, the heterozygous (CT) genotype of rs11886868 exhibited a significant association with thalassemia risk (approximately two-fold increased risk. Analysis of both genotypes together revealed a marginally significant association (one-fold increased risk) with thalassemia in individuals carrying any variant allele of rs11886868. The allelic distribution of the rs1427407 SNP of BCL11A indicated that the heterozygous (GT) genotype of this SNP was significantly associated with thalassemia (approximately two-fold increased risk, with respect to the control group). Combining all genotypes into a joint model confirmed a significant association between the presence of any variant allele of rs1427407 and thalassemia (two-fold increased risk). The genotypic distribution frequencies of the heterozygous (CT) genotype for the rs9399137 SNP of HBS1L-MYB was similar to that of rs1427407, and exhibited a highly significant association with thalassemia risk (nearly two-fold increased risk). Analysis of both genotypes together revealed a significant association with thalassemia risk (one-fold increase) for individuals carrying any variant allele of rs9399137. CONCLUSION: BCL11A and HBS1L-MYB polymorphisms were significantly associated with increased thalassemia risk.