Journal Article

Susceptibility to sequelae of human ocular chlamydial infection associated with allelic variation in <i>IL10 cis</i>-regulation

Angels Natividad, Martin J. Holland, Kirk A. Rockett, Julian Forton, Nkoyo Faal, Hassan M. Joof, David C.W. Mabey, Robin L. Bailey and Dominic P. Kwiatkowski

in Human Molecular Genetics

Volume 17, issue 2, pages 323-329
Published in print January 2008 | ISSN: 0964-6906
Published online October 2007 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddm310
Susceptibility to sequelae of human ocular chlamydial infection associated with allelic variation in IL10 cis-regulation

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Trachoma, an infectious disease of the conjunctiva caused by Chlamydia trachomatis, causes scarring and blindness in some infected individuals but not others. In an African community where trachoma is endemic, we have previously identified an IL10 haplotype that is associated with increased risk of scarring complications. Here we examine the hypothesis that the risk haplotype (H-RISK) affects levels of IL10 expression in the conjunctiva during active trachoma infection. To overcome potential genetic and environmental confounders we used the method of allele-specific quantification, which involved identifying subjects in the community who had active trachoma and were also heterozygous for the H-RISK. We find that there is allelic variation in cis-regulation of IL10 in the conjunctiva during active trachoma, with the H-RISK generating relatively more IL10 transcripts than other haplotypes in this population (average difference in IL10 allelic transcripts in the conjunctiva of heterozygous individuals infected with C. trachomatis of 23% (95% confidence interval: 14–32%, P < 0.0001). These findings provide a plausible functional explanation for the observed genetic association, and support the hypothesis that an excessive IL10 response to C. trachomatis infection is a risk factor for scarring and blindness.

Journal Article.  4272 words.  Illustrated.

Subjects: Genetics and Genomics

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