Modulating Influence on HIV/Aids by Interacting RANTES Gene Variants

Authors

• Ping An, National Cancer Institute at Frederick
• George W. Nelson, National Cancer Institute at Frederick
• Lihua Wang, National Cancer Institute at Frederick
• Sharyne Donfield, Rho, Inc.
• James J. Goedert, National Cancer Institute at Rockville
• John Phair, Northwestern University Medical School
• David Vlahov, Johns Hopkins Bloomberg School of Public Health
• Susan Buchbinder, San Francisco Department of Public Health
• William L. Farrar, National Cancer Institute at Frederick
• William Modi, National Cancer Institute at Frederick
• Stephen J. O'Brien, National Cancer Institute at FrederickFollow
• Cheryl Winkler, National Cancer Institute at Frederick

ORCID

0000-0001-7353-8301

ResearcherID

N-1726-2015

Document Type

Article

Publication Title

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

ISSN

1091-6490

Publication Date

7-23-2002

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 3′222C 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.

Volume

99

Issue

15

First Page

10002

Last Page

10007

Comments

© 2002, The National Academy of Sciences

Additional Comments

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

NSUWorks Citation

An, Ping; George W. Nelson; Lihua Wang; Sharyne Donfield; James J. Goedert; John Phair; David Vlahov; Susan Buchbinder; William L. Farrar; William Modi; Stephen J. O'Brien; and Cheryl Winkler. 2002. "Modulating Influence on HIV/Aids by Interacting RANTES Gene Variants." Proceedings of the National Academy of Sciences of the United States of America 99, (15): 10002-10007. https://nsuworks.nova.edu/cnso_bio_facarticles/225