Susceptibility Genes, Environmental Risk Factors And Their Interactions In The Development Of Pulmonary Tuberculosis

The development of tuberculosis (TB) is due to interactions between host genes and environmental risk factors in a complex way. In the current case control study, the polymorphisms in Vitamin D receptor (VDR) gene, natural-resistance-associated macrophage protein 1(NRAMP 1) gene and mannose-binding lectin (MBL) gene were examined to assess their contribution to pulmonary tuberculosis(P.tb) in Chinese Han population. In addition, possible interactions between host genes and environmental factors were explored.Two functionally characterized genotypes in NRAMPl gene (D543N-GA and 3'UTR- TGTG+/del) and the XB haplotype group in MBL gene were found to be significantly associated with increased risk of P.tb, while the MBL-HL and LL genotyes were significantly associated with decreased risk of the disease. The gene-environment interaction analyses disclosed positive statistical interactions between NRAMPI gene D543N-GA, 3'UTR- TGTG+/del genotypes and exposure history in the occurrence of P.tb. In addition, significant interactions existed between MBL-HL, LL genotypes and BCG vaccination in the protection of the disease. None of the other gene-environment interaction was statistically significant.We then made functional analyses of four MBL gene haplotypes using luciferase reporter assay, and found the haplotypes of HYP, LYP, LYQ and LXP demonstrated decreasing promoter activities, which might in part explain their differential roles in the disease susceptibility.The present paper also reported three TB patients coinfected with severe acute respiratory syndrome (SARS) and described the viral excretion pattern and one-year follow-up immune responses by a prospective study. The comparison with normal...