CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

Background: Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1 alpha and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1 alpha, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1 alpha and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Methods and results: Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0-6 copies per diploid genome (pdg) in Peru, between 0-12 pdg in !Xhosa samples and between 0-10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). Conclusions: The case-control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1 alpha or CCR5 individually or together in susceptibility to clinically active TB in these populations.