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

Autor: Tang NL; Department of Chemical Pathology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China. nelsontang@cuhk.edu.hk, Fan HP, Chang KC, Ching JK, Kong KP, Yew WW, Kam KM, Leung CC, Tam CM, Blackwell J, Chan CY
Jazyk: angličtina
Zdroj: Clinica chimica acta; international journal of clinical chemistry [Clin Chim Acta] 2009 Aug; Vol. 406 (1-2), pp. 98-102. Date of Electronic Publication: 2009 Jun 10.
DOI: 10.1016/j.cca.2009.06.006
Abstrakt: 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 chi(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 14bp 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.
Databáze: MEDLINE
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