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Haplotype analysis of the SDF-1 (CXCL12) gene in a longitudinal HIV-1/AIDS cohort study.

Modi WS, Scott K, Goedert JJ, Vlahov D, Buchbinder S, Detels R, Donfield S, O'brien SJ, Winkler C

SAIC Frederick, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA.

The stromal-derived factor-1 (SDF-1) chemokine gene encodes the only natural ligand for CXCR4, the coreceptor for the pathogenic X4 HIV-1 strains. A single-nucleotide polymorphism (SNP) in the 3' untranslated region (SDF1-3'A=rs1801157) of SDF-1 was reported to be protective against infection and progression in some, but not other, epidemiological studies. To identify additional alleles that may influence HIV-1 infection and progression to AIDS, nine SNPs (including rs1801157) spanning 20.2 kb in and around the SDF-1 gene were genotyped in over 3000 African American (AA) and European American (EA) participants enrolled in five longitudinal HIV-1/AIDS natural cohort studies. Six or five haplotypes were present at frequencies greater than 5% in AA or EA, respectively. Six of the nine SNPs occur on only one common haplotype (>5%), while the remaining three SNPs were found on multiple haplotypes, suggesting a complex history of recombination. Among EA, rs754618 was associated with an increased risk of infection (OR=1.50, P=0.03), while rs1801157 (=SDF1-3'A) was associated with protection against infection (OR=0.63, P=0.01). In the MACS cohort, rs1801157 was associated with AIDS-87 (RH=0.31, P=0.02) and with death (RH=0.18, P=0.02). Significant associations to a single disease outcome were found for two SNPs and one haplotype in AA.

Published 1 December 2005 in Genes Immun, 6(8): 691-8.
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