P2X sub(7) and NRAMP1SLC11 A1 gene polymorphisms in Mexican mestizo patients with pulmonary tuberculosis

Tuberculosis remains one of the most important infectious diseases worldwide. Several studies have suggested that genetic factors may affect susceptibility to tuberculosis, but the specific genes involved have not yet been fully characterized. NRAMP1SLC11 A1 and P2X sub(7) genes have been linked to increased risk for tuberculosis in some African and Asiatic populations. To explore the potential role of these genes in the susceptibility to pulmonary tuberculosis in a Mexican mestizo population, we evaluated the association of D543N and 3'-UTR polymorphisms in NRAMP1SLC11 A1 and - 762 and A1513C polymorphisms in P2X sub(7) genes with the risk for tuberculosis. Polymerase chain reaction (PCR) amplification of genomic DNA followed by restriction fragment length polymorphism analysis, and allelic-specific PCR was employed. We found no significant differences in allelic frequency in NRAMP1SLC11 A1 gene polymorphisms in 94 patients with tuberculosis compared to 100 healthy contacts. Similarly, no significant association of the P2X sub(7)-762 gene polymorphism with tuberculosis was detected. In contrast, the P2X sub(7) A1513C polymorphism was associated significantly with tuberculosis (P = 0.02, odds ratio = 5.28, 95% CI, 0.99-37.69), an association that had not been reported previously. However, when the function of P2X sub(7) was assessed by an l-selectin loss assay, we did not find significant differences in patients compared to healthy contacts or between PPD super(+) and PPD super(-) control individuals. This study further supports the complex role of P2X sub(7) gene in host regulation of Mycobacterium tuberculosis infection, and demonstrates that different associations of gene polymorphisms and tuberculosis are found in distinct racial populations.