Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression

Srinivas Mummidi, Seema S. Ahuja, Enrique Gonzalez, Stephanie A. Anderson, Elvin N. Santiago, Kevin T. Stephan, Fiona E. Craig, Peter O'Connell, Victor Tryon, Robert A. Clark, Matthew J. Dolan, Sunil K. Ahuja

Producción científica: Articlerevisión exhaustiva

304 Citas (Scopus)

Resumen

Allelic variants for the HIV-1 co-receptors chemokine receptor 5 (CCRS) and CCR2, as well as the ligand for the co-receptor CXCR4, stromal-derived factor (SDF-1), have been associated with a delay in disease progression. We began this study to test whether polymorphisms in the CCR5 regulatory regions influence the course of HIV-1 disease, as well as to examine the role of the previously identified allelic variants in 1,090 HIV-1 infected individuals. Here we describe the evolutionary relationships between the phenotypically important CCR5 alleles, define precisely the CCR5 regulatory sequences that are linked to the CCRS-Δ32 and CCR2-641 polymorphisms, and identify genotypes associated with altered rates of HIV-1 disease progression. The disease-retarding effects of the CCR2-641 allele were found in African Americans but not in Caucasians, and the SDF1-3'A/3'A genotype was associated with an accelerated progression to death. In contrast, the CCR5-Δ32 allele and a CCR5 promoter mutation with which it is tightly linked were associated with limited disease-retarding effects. Collectively, these findings draw attention to a complex array of genetic determinants in the HIV-host interplay.

Idioma originalEnglish (US)
Páginas (desde-hasta)786-793
Número de páginas8
PublicaciónNature Medicine
Volumen4
N.º7
DOI
EstadoPublished - jul 1998

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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