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

Abstract
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.
AuthorsW S Modi, K Scott, J J Goedert, D Vlahov, S Buchbinder, R Detels, S Donfield, S J O'brien, C Winkler
JournalGenes and immunity (Genes Immun) Vol. 6 Issue 8 Pg. 691-8 (Dec 2005) ISSN: 1466-4879 [Print] England
PMID16177829 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
Topics
  • Acquired Immunodeficiency Syndrome (epidemiology, genetics, mortality)
  • Adolescent
  • Adult
  • African Americans (genetics, statistics & numerical data)
  • Alleles
  • Chemokine CXCL12
  • Chemokines, CXC (genetics)
  • Child
  • Cohort Studies
  • Disease Progression
  • European Continental Ancestry Group (genetics, statistics & numerical data)
  • Female
  • Gene Frequency
  • HIV Infections (epidemiology, genetics)
  • HIV-1 (genetics)
  • Haplotypes
  • Humans
  • Longitudinal Studies
  • Male
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Survival Analysis
  • United States (epidemiology)

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