Biology Faculty Articles

Title

MCP-1-MCP-3–Eotaxin Gene Cluster Influences HIV-1 Transmission

Document Type

Article

Publication Date

11-7-2003

Publication Title

AIDS

Keywords

HIV-1 transmission, MCP-1, MCP-3, Eotaxin, Immune system activation

ISSN

0269-9370

Volume

17

Issue/No.

16

First Page

2357

Last Page

2365

Abstract

Background: MCP-1 (CCL2), MCP-3 (CCL7), and eotaxin (CCL11) are genes for CC chemokines clustered on the long arm of chromosome 17. Previous studies have implicated these chemokines in monocyte recruitment, viral replication, and anti-HIV cytotoxic T cell responses. An epidemiological analysis identified genetic variants influencing HIV-1 transmission and disease progression.

Methods: Genomic DNA from over 3000 participants enrolled in five natural history cohorts in the United States were analyzed. Nine single nucleotide polymorphisms (SNP) covering 33 kb containing these three genes were genotyped using the polymerase chain reaction. Distortions in allele, genotype, and haplotype frequencies were assessed with respect to HIV-1 transmission and rates of disease progression using categorical and survival analyses.

Results: Extensive linkage disequilibrium was observed. Three SNP (−2136T located in theMCP-1 promoter region, 767G in intron 1 of MCP-1, and −1385A in the Eotaxin promoter) were nearly always found together on a 31 kb haplotype (H7) containing the three genes. Frequencies of the three variants and the H7 haplotype were significantly elevated (odds ratio, 0.6; P = 0.005–0.01) in uninfected European-Americans repeatedly exposed to HIV-1 through high-risk sexual behavior or contaminated blood products.

Conclusions: Although the extensive linkage disequilibrium precludes positive identification of the causal variant, the results suggest that genetic variation in the H7 region influences susceptibility to HIV-1 infection. Since these chemokines do not bind the primary HIV-1 coreceptors CCR5 or CXCR4, the observed influence on transmission may result from activation of the immune system in response to infection rather than receptor blockage.

Comments

© 2003 Lippincott Williams & Wilkins, Inc.

Additional Comments

GenBank accession #: AC005549

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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