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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&gt;1 ( P &lt;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.

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