title: A single nucleotide polymorphism (A --> G) in intron 3 of IFNgamma gene is associated with asthma.
abstract: Interferon-gamma (IFNgamma) is located on chromosome 12, and a number of studies have detected very strong linkage signals around this gene and asthma. The aim of this study was to analyze the association of a (CA)n repeat in intron 1 and six single nucleotide polymorphisms (((rs2069705, T/C) (promoter)), ((rs1861494, A/G), (rs1861493, T/C), (rs2069718, C/T) (intron 3)), ((rs2069727, A/G) and (rs2069728, G/A) (3' untranslated region))) spanning the whole gene with asthma. We report here the association of rs1861494 A/G with atopic asthma in a case-control cohort (n=189 and n=270 cases and controls, respectively) (P=0.0006), which was replicated (P=0.006) in a family study (n=137) as well. Allele G was found to be negatively associated (odds ratio=0.50, 95% confidence interval, P=0.0006). A five-locus haplotype also showed significant association with asthma in the case-control (P=0.002) and the family studies (P=0.0004). In our three-locus sliding window haplotypic analysis, we found the (CA)n repeat, rs1861494 A/G and rs2069718 C/T to be of high priority (P=0.0003). Using electrophoretic mobility shift assay, we provide evidence that the alleles of rs1861494 A/G have differential affinity to bind to putative nuclear factor(s). In conclusion, we report for the first time association of rs1861494 A/G polymorphism with asthma, which may regulate the IFNgamma levels and, hence, modulate asthma pathogenesis.
authors.affiliation: Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: B
authors.initials: B
authors.lastname: Ghosh
mesh_terms: D000328:Adult; D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12; D015331:Cohort Studies; D024202:Electrophoretic Mobility Shift Assay; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics*; D007438:Introns; D015810:Linkage Disequilibrium; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
chemical_list: D007073:Immunoglobulin E; D007371:Interferon-gamma