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Human Molecular Genetics Advance Access originally published online on October 18, 2007
Human Molecular Genetics 2008 17(2):323-329; doi:10.1093/hmg/ddm310
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Angels Natividad1,2,*, Martin J. Holland1,3, Kirk A. Rockett2, Julian Forton2, Nkoyo Faal3, Hassan M. Joof3, David C.W. Mabey1, Robin L. Bailey1 and Dominic P. Kwiatkowski2

1 Infectious and Tropical Diseases Department, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK 2 Childhood Infection, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK 3 Virology Department, Medical Research Council Laboratories, Fajara, The Gambia

* To whom correspondence should be addressed at: Clinical Research Unit, Infectious Tropical Disease Department, London School of Hygiene and Tropical Medicine, Room 246, Keppel Street, London WC1E 7HT, UK. Tel: +44 (0)2079272195; Fax: +44 (0)2076374314; Email: angels.natividad-sancho{at}lshtm.ac.uk

Received September 3, 2007; Accepted October 16, 2007

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.


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