Distribution of HLA-A, B and DRB1 alleles in Sahariya tribe of North Central India: An association with pulmonary tuberculosis

Abstract

Sahariya, a primitive tribe, native of North Central India, is characterized by a significantly increased incidence of pulmonary tuberculosis (PTB) as compared to other tribes from the same region. Host genetic factors are known to influence susceptibility to PTB at the population level. Since an association of immune regulatory genes, particularly HLA, with PTB susceptibility has already been reported in several studies, we investigated a similar association of HLA alleles with PTB pathogenesis in the Sahariya tribe. A total of 210 cases and 178 healthy individuals from Sahariya tribe were genotyped for HLA class I and II alleles using the PCR based SSP and Reverse-SSO methods. The study showed a significantly increased allelic frequency of HLA-DRB1∗15 (p=0.02) in the patients as compared to healthy controls. However, the allelic frequency of HLA-DRB1∗16 was significantly reduced in patients than in controls (p=0.01). Three locus haplotype analysis of HLA-A, B and DR revealed a significantly increased frequency of A∗24-B∗40-DRB1∗15 haplotype among patients than controls (p=0.005), while A∗02-B∗40-DRB1∗16 and A∗02-B40-DRB1∗03 (p=0.001 and 0.02, respectively) were significantly reduced in the patients. Our findings confirm a positive association of HLA-DRB1∗15 in Sahariya tribe similar to the one already shown in other Indian ethnic groups. On the other hand, HLA-A∗24-B∗40-DRB1∗15 haplotype was found to be specific to Sahariya tribe with a strong predisposition to PTB. Further, the protection offered by DRB1∗16 allele and associated haplotypes towards PTB in this tribe appears to be a novel finding that warrants further investigation with regard to resistance to PTB.