Low expression alleles and tuberculosis in HIV infected South Africans.

Host immunity is crucial for controlling infection. Functional polymorphisms in the cytokine macrophage migration inhibitory factor (MIF) show global population stratification, with the highest prevalence of low expression alleles found in sub-Saharan Africans, which is a population with the greatest confluence of both TB and HIV infection and disease. We investigated the association between alleles and tuberculosis (TB) and HIV in South Africa. We acquired clinical information and determined the frequency of two promoter variants: a functional -794 CATT microsatellite and an associated -173 G/C SNP in two HIV-positive cohorts of patients with active laboratory-confirmed TB and in controls without active TB who were all HIV positive. We found a greater frequency of low expression promoter variants (-794 CATT) among TB disease cases compared to controls (OR = 2.03, p = 0.023), supporting a contribution of genetic low expression to the high prevalence of TB in South Africa. Among those with HIV, circulating MIF levels also were associated with lower CD4 cell counts irrespective of TB status (p = 0.016), suggesting an influence of HIV immunosuppression on expression.