Abstract
Interleukin-10 (IL-10) is a pleiotropic cytokine with both immunosuppressive and immunostimulatory functions. Its roles in infections and autoimmunity may have resulted in selective pressures on polymorphisms within the gene, leading to genomic coexistence of several semi-conserved haplotypes involved with diverse pathogen interactions during genomic evolution. Previous studies focused either exclusively on promoter haplotypes or on individual SNPs. We genotyped 21 single nucleotide polymorphisms in the human IL10 gene and examined this variation compared to other mammalian species sequences. Haplotype heterogeneity in human populations is centered around 'classic' 'proximal' promoter polymorphisms: -592, -819 and -1082. High-producing GCC haplotypes are by far the most numerous and diverse group, the intermediate IL-10 producing ACC-inclusive haplotypes seem to be related most closely to the ancestral haplotype, and the ATA-inclusive haplotypes cluster a separate branch with strong bootstrap support. We looked at associations of corresponding haplotypes with HIV progression. A haplotype trend regression confirmed that individuals carrying the low-producing ATA-inclusive haplotypes in European Americans progress to AIDS faster, and most likely explain the role of IL10. Our findings are consistent with the hypothesis that existing polymorphisms in this gene may reflect a balance of historic adaptive responses to autoimmune, infectious and other disease agents.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 309-322 |
| Number of pages | 14 |
| Journal | Genes and Immunity |
| Volume | 10 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2009 |
Funding
We thank the patients and staff of all the participating cohorts in the study. We thank Drs Cheryl Winkler, Michael Dean and Mary Carrington for helpful insights in developing the ideas for this paper. We are also grateful to Bailey Kessing, Michael Malasky and Mary Thompson for their assistance. We thank Maritta Grau and Allen Kane of Scientific Publications, Graphics and Media, SAIC-Frederick Inc., for help with the study preparation. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does it mention of trade names, commercial products, or organizations, which imply the endorsement by the US government. The project included in this paper has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400.
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
- Immunology
