Title

Extended IL10 Haplotypes and their Association with HIV Progression to AIDS

Authors

T. K. Oleksyk, National Cancer Institute at Frederick; University of Alabama - Birmingham
Sadeep Shrestha, University of Alabama - Birmingham
Ann L. Truelove, National Cancer Institute at Frederick
James J. Goedert, National Cancer Institute at Bethesda
Sharyne Donfield, Rho, Inc.
John Phair, Northwestern University Medical School
Shruti Mehta, Johns Hopkins University
Stephen J. O'Brien, National Cancer Institute at FrederickFollow
M. W. Smith, National Cancer Institute at Frederick

Document Type

Article

Publication Date

6-2009

Publication Title

Genes and Immunity

Keywords

AIDS, HIV progression, IL-10 protein, IL10 gene, Promoter haplotypes

ISSN

1466-4879

Volume

10

Issue/No.

4

First Page

309

Last Page

322

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.

Comments

©2009 Macmillan Publishers Limited All rights reserved

Additional Comments

National Cancer Institute contract #: N01-CO-12400

NSUWorks Citation

Oleksyk, T. K.; Sadeep Shrestha; Ann L. Truelove; James J. Goedert; Sharyne Donfield; John Phair; Shruti Mehta; Stephen J. O'Brien; and M. W. Smith. 2009. "Extended IL10 Haplotypes and their Association with HIV Progression to AIDS." Genes and Immunity 10, (4): 309-322. https://nsuworks.nova.edu/cnso_bio_facarticles/469

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015