¹Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Delhi, India

Correspondence: Dr B Ghosh, Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Near Jubilee Hall Hostel, Delhi University Campus, Mall Road, Delhi 110007, India. E-mail: bghosh@igib.res.in

Received 28 December 2007; Revised 18 February 2008; Accepted 19 February 2008; Published online 3 April 2008.

Abstract

Interferon-gamma (IFN) 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 IFN levels and, hence, modulate asthma pathogenesis.