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


CONCLUSIONS
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.
Tang
Nelson Leung-Sang
NL
Department of Chemical Pathology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China. nelsontang@cuhk.edu.hk
Fan
Harris Pok Yin
HP
Chang
Kwok Chiu
KC
Ching
Jasmine Kuk Lai
JK
Kong
Kathy Pui Shan
KP
Yew
Wing Wai
WW
Kam
Kai Man
KM
Leung
Chi Chiu
CC
Tam
Cheuk Ming
CM
Blackwell
Jenefer
J
Chan
Chiu Yeung
CY
D054357:Chemokine CXCL10 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics*
D054357:Chemokine CXCL10