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Human Molecular Genetics Advance Access originally published online on June 15, 2004
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Human Molecular Genetics, 2004, Vol. 13, No. 16 1755-1762
DOI: 10.1093/hmg/ddh187
Human Molecular Genetics, Vol. 13, No. 16 © Oxford University Press 2004; all rights reserved

Transcription of the IL10 gene reveals allele-specific regulation at the mRNA level

Fina A.S. Kurreeman1,{dagger}, Joris J.M. Schonkeren1,{dagger}, Bastiaan T. Heijmans2, Rene E.M. Toes1 and Tom W.J. Huizinga1,*

1Department of Rheumatology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands and 2Department of Molecular Epidemiology, Leiden University Medical Centre, PO Box 9503, 2300 RA Leiden, The Netherlands

Received April 8, 2004; Accepted June 8, 2004

Interleukin-10 (IL10) is a cytokine with key regulatory and anti-inflammatory function involved in the pathogenesis of various diseases. Although the large interindividual differences in the production of IL10 have been extensively associated with polymorphisms and haplotypes of the IL10 gene, surprisingly little evidence exists that this variation is actually dictated by IL10 haplotypes. Using the technique of allele-specific transcript quantification, the ratio between two alleles (A and G) of the IL10 gene was characterized in 15 healthy heterozygous individuals. Two groups were identified whereby donors in group 1 exhibited a 1 : 1 ratio, whereas those in group 2 exhibited a ratio>1 (P<0.0017). We found that donors heterozygous for haplotype IL10.2 (one of the four ancient IL10 haplotypes) were only prevalent in the group that showed higher allelic expression ratios. In this study we show that IL10 alleles are indeed differentially transcribed in cells from heterozygous individuals and that IL10 haplotypes dictate production of IL10. These findings show that interindividual differences in IL10 protein levels can be explained at the transcriptional level.

* To whom correspondence should be addressed. Email: t.w.j.huizinga{at}lumc.nl


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