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Human Molecular Genetics Advance Access published online on October 18, 2007
Human Molecular Genetics, 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 IL-10 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, United Kingdom 2 Childhood Infection, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom 3 Virology Department, Medical Research Council Laboratories, Fajara, The Gambia

* Angels Natividad Room 246, Clinical Research Unit, Infectious Tropical Disease Department, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK Phone: +44 (0)2079272195 FAX: +44 (0)2076374314 Email: angels.natividad-sancho{at}lshtm.ac.uk

Received September 3, 2007; Revised October 16, 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 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 risk haplotype. We find that there is allelic variation in cis-regulation of IL10 in the conjunctiva during active trachoma, with the risk haplotype 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 Chlamydia 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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