Genetic polymorphisms of CCL2, CCL5, CCR2 and CCR5 genes in Sahariya tribe of North Central India: An association study with pulmonary tuberculosis

The association of genetic variants of chemokines, CCL2 [. MCP-1 (monocyte chemoattractant protein-1)], CCL5 [. RANTES (regulated on activation, normal T-cell expressed and secreted)] and their receptors CCR2 and CCR5, respectively, earlier reported to be associated with susceptibility to pulmonary tuberculosis (PTB) in certain ethnic populations, were explored in Sahariya tribe, a primitive tribe of North Central India having a high prevalence of TB. We genotyped 215 cases and 215 controls of Sahariya tribe for polymorphisms in CCL2 (-2518A/G, -362G/C) by PCR-RFLP method and in CCR2 (V64I), CCL5 (-403G/A, -28C/G) and CCR5 (-59029G/A) by ARMS-PCR method. The frequencies of 'AA' genotype and 'A' allele of -403G/A were found significantly higher in cases than in controls (OR, 2.616 [95%CI, 1.302-5.320] and OR, 1.348 [95%CI, 0.980-1.853], respectively). Conversely, the frequencies of 'AA' genotype and 'A' allele of V64I were significantly (p= 0.05 and 0.04, respectively) higher in controls than in cases. Also, the "AA" genotype of V64I was found to provide significant (p= 0.05) protection against high bacillary load (3+). Likewise, the comparison of frequencies of different combinations of these polymorphisms further strengthens the association of -403G/A with susceptibility and V64I with resistance to TB in Sahariya tribe. However, no significant association of other polymorphisms with either resistance or susceptibility to TB was found. Thus, our findings support the association of -403G/A and V64I polymorphisms with genetic susceptibility and resistance to TB, respectively, alone or in combination with other polymorphisms in Sahariya tribe.