Genetic polymorphism of novel SNP rs5006884 in OR51B6 and SNP rs4499252 in AHSP among transfusion-dependent and non-transfusion-dependent β-thalassemia/Hb E patients in Thailand: a multivariate analysis of clinical and genetic polymorphism

Abstract

Compound heterozygous β-thalassemia and Hb E, a prevalent and severe form of thalassemia in Southeast Asia, manifests in two major clinical forms: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). This study investigates the association of genetic polymorphisms rs5006884 in OR51B6, rs4499252 in AHSP, rs9399137 in HBS1L-MYB, and rs4671393 in BCL11A with clinical severity and transfusion dependency in β-thalassemia/Hb E patients in Thailand. A total of 189 samples, including 58 TDT, 58 NTDT, 33 homozygous Hb E, and 40 wild-type individuals, were analyzed. Genotyping of the four single nucleotide polymorphisms (SNPs) was conducted using the rhAmp SNP Genotyping assay. Multivariate regression models were developed to evaluate the combined effects of genetic and clinical factors on transfusion dependency. The results showed that OR51B6 SNP rs5006884 TT genotype was significantly more frequent in the NTDT group (P < 0.05), suggesting a strong association with reduced transfusion dependency. Conversely, the AHSP SNP rs4499252 GG genotype was significantly less frequent in the homozygous Hb E group (P < 0.05) compared to other groups. Multivariate analyses highlighted hemoglobin (Hb) levels as a robust predictor of transfusion dependency, with specific HBB mutations including HBB:c.59 A > G, HBB:c.-78 A > G, HBB:c.316–197 C > T, and NC_000011.10:g.5224302_5227791del being significantly associated with NTDT (P < 0.05). Furthermore, rs5006884 in OR51B6 also played a significant role in NTDT in multivariate analyses. In contrast, SNPs in BCL11A (rs4671393), HBS1L-MYB (rs9399137), and AHSP (rs4499252) showed no significant independent associations with transfusion dependency or disease severity in this cohort. This study explores rs5006884 in OR51B6 and rs4499252 in AHSP in TDT and NTDT patients for the first time. These findings elucidate the interplay of genetic and clinical factors influencing β-thalassemia severity, paving the way for personalized management strategies to mitigate transfusion requirements.