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A single nucleotide polymorphism (A → G) in intron 3 of IFNγ gene is associated with asthma

Genes & Immunity volume 9, pages 294–301 (2008)Cite this article

Abstract

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

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Acknowledgements

We acknowledge the Indian Council of Medical Research (project code GAP9114), Government of India, for financial assistance. AK acknowledges CSIR for his fellowship. We thank all participating clinicians and volunteers for helping in this study and patients and their family members for participating. We also thank Ms Jyotsna Batra, Mr Rajshekhar Chatterjee, Dr Shilpy Sharma and Dr Rana Nagarkatti for their help.

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

    A Kumar & B Ghosh

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Correspondence to B Ghosh.

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Kumar, A., Ghosh, B. A single nucleotide polymorphism (A → G) in intron 3 of IFNγ gene is associated with asthma. Genes Immun 9, 294–301 (2008). https://doi.org/10.1038/gene.2008.17

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