title: Genetic association between a chemokine gene CXCL-10 (IP-10, interferon gamma inducible protein 10) and susceptibility to tuberculosis.
abstract: 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.
authors.affiliation: Department of Chemical Pathology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China. nelsontang@cuhk.edu.hk
authors.forename: Nelson Leung-Sang
authors.initials: NL
authors.lastname: Tang
authors.forename: Harris Pok Yin
authors.initials: HP
authors.lastname: Fan
authors.forename: Kwok Chiu
authors.initials: KC
authors.lastname: Chang
authors.forename: Jasmine Kuk Lai
authors.initials: JK
authors.lastname: Ching
authors.forename: Kathy Pui Shan
authors.initials: KP
authors.lastname: Kong
authors.forename: Wing Wai
authors.initials: WW
authors.lastname: Yew
authors.forename: Kai Man
authors.initials: KM
authors.lastname: Kam
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Leung
authors.forename: Cheuk Ming
authors.initials: CM
authors.lastname: Tam
authors.forename: Jenefer
authors.initials: J
authors.lastname: Blackwell
authors.forename: Chiu Yeung
authors.initials: CY
authors.lastname: Chan
mesh_terms: 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*
chemical_list: D054357:Chemokine CXCL10