Biology Faculty Articles

Title

Modulating Influence on HIV/Aids by Interacting RANTES Gene Variants

Document Type

Article

Publication Date

7-23-2002

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

ISSN

1091-6490

Volume

99

Issue/No.

15

First Page

10002

Last Page

10007

Abstract

RANTES (regulated on activation normal T cell expressed and secreted), a ligand for the CC chemokine receptor 5, potently inhibits HIV-1 replication in vitro. We tested the influence of four RANTES single nucleotide polymorphism (SNP) variants and their haplotypes on HIV-1 infection and AIDS progression in five AIDS cohorts. Three SNPs in the RANTES gene region on chromosome 17 (403A in the promoter, In1.1C in the first intron, and 3222C in the 3′ untranslated region) are associated with increased frequency of HIV-1 infection. The common In1.1C SNP allele is nested within an intronic regulatory sequence element that exhibits differential allele binding to nuclear proteins and a down-regulation of gene transcription. The In1.1C allele or haplotypes that include In1.1C display a strong dominant association with rapid progression to AIDS among HIV-1-infected individuals in African-American, European-American, and combined cohorts. The principal RANTES SNP genetic influence on AIDS progression derives from the down-regulating RANTES In1.1C allele, although linkage disequilibrium with adjoining RANTES SNPs including a weaker up-regulating RANTES promoter allele (−28G), can modify the observed epidemiological patterns. The In1.1C-bearing genotypes account for 37% of the attributable risk for rapid progression among African Americans and may also be an important influence on AIDS progression in Africa. The diminished transcription of RANTES afforded by the In1.1C regulatory allele is consistent with increased HIV-1 spread in vivo, leading to accelerated progression to AIDS.

Comments

© 2002, The National Academy of Sciences

Additional Comments

NIH Contract #NO1-CO-12400; _x000D_ GenBank Accession #s: AF336300, AF336301

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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