Association of Predisposing Haplotype Snp-Markers of HBB Gene in Thalassaemia

Abstract

Most of the beta thalassaemia cases are heterogeneous at the molecular level. The genetic variation arises due to the mutation of a single beta-globin gene (HBB) on chromosome 11p15.5. Eventhough, the basis and natural history of this disorder are still not well understood and the clinical presentation in certain patients was not always correlated well with the single gene diagnosis [1].
 
 The study aimed to evaluate the predisposing effect of HBB polymorphisms and their haplotypes in conferring beta-thalassaemia in Malaysia using a bioinformatics tool. Archived genotype data for five tagging SNPs of HBB gene assigned as c.9T/C, IVS2-16G/C, IVS2-74T/G, 3'UTR +314G/A and 3'UTR +316A/C across thalassaemia patient group (n=433) and normal control group (n=794) controls were retrieved from the year 2011 to 2016 at Institute for Medical Research (IMR). The genotype data were analysed for individual SNP-based association analysis and haplotype-based association analysis using SHEsis online software.
 
 The study in all races in Malaysia showed significant association in four SNPs of the HBB gene (c.9T/C, P-value = 0.014; IVS2-16G/C, P-value = 0.017; 3'UTR+314G/A, P value = 2.08x108; 3'UTR+316A/C, P-value = 0.021). However, IVS2-74T/G did not show significant association with a P-value of 0.763 (Table 1). We further revealed two susceptible haplotypes in all races (haplotype TGTAA, P-value = 1.68x10-7, OR = 2.382 [1.707~3.325]; haplotype CCTGC, P-value = 0.003, OR = 1.300 [1.089~1.551]). Meanwhile, one protective haplotype observed was haplotype TGTGA (P-value = 2.99x10-7, OR = 0.625 [0.522~0.749]) (Table 2).
 In conclusion, this study suggests the potential susceptible and protective haplotypes of the HBB gene in predisposing to beta-thalassaemia in Malaysia