Genetic association between a chemokine gene CXCL-10 (IP-10, interferon gamma inducible protein 10) and susceptibility to tuberculosis

Tang, Nelson Leung-Sang; Fan, Harris Pok Yin; Chang, Kwok Chiu; Ching, Jasmine Kuk Lai; Kong, Kathy Pui Shan; Yew, Wing Wai; Kam, Kai Man; Leung, Chi Chiu; Tam, Cheuk Ming; Blackwell, Jenefer; Chan, Chiu Yeung

BACKGROUND: Previous studies showed that activation of CXCL-10 and other chemokines were prominent in many infectious diseases. These chemokines are components of innate immune response to respiratory tract pathogens. We examined the promoter variants of CXCL-10 and their role in predisposition to tuberculosis (TB). METHODS: The promoter 1.8 kb of CXCL-10 was sequenced in 24 healthy Chinese individuals to identify genetic polymorphisms. Three tagging SNPs in CXCL-10 promoter (− 1447A > G, − 872G > A, − 135G > A) were selected, and genotyping were performed in 240 TB patients and 176 healthy Chinese subjects. Disease associations were examined by χ(2) and Fisher exact test. RESULTS: A promoter SNP (− 135G > A) with minor allele frequency of 0.1 showed a moderate association with TB both in genotype analysis (p = 0.01) and allelic analysis (p = 0.03); other tagging SNPs (− 1447A > G, − 872G > A) were not associated with TB. The odd ratio of the protective allele − 135G > A was 0.51(C.I 0.29 − 0.91) for homozygotes and heterozygotes carriers of the A allele. CONCLUSION: A new potential protective SNP (− 135G > A) for TB is identified in the promoter of chemokine gene, CXCL-10. Interestingly, the exact same allele has been shown to enhance IP-10 transactivation and susceptibility to Hepatitis B virus infection in a recent publication. This SNP, located at 14 bp upstream of a NF-kB binding site, might also account for the susceptibility to TB. Our results expanded the clinical significance of this SNP in CXCL-10 promoter.