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.
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Authors | W S Modi, K Scott, J J Goedert, D Vlahov, S Buchbinder, R Detels, S Donfield, S J O'brien, C Winkler |
Journal | Genes and immunity
(Genes Immun)
Vol. 6
Issue 8
Pg. 691-8
(Dec 2005)
ISSN: 1466-4879 [Print] England |
PMID | 16177829
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- CXCL12 protein, human
- Chemokine CXCL12
- Chemokines, CXC
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Topics |
- Acquired Immunodeficiency Syndrome
(epidemiology, genetics, mortality)
- Adolescent
- Adult
- Black or African American
(genetics, statistics & numerical data)
- Alleles
- Chemokine CXCL12
- Chemokines, CXC
(genetics)
- Child
- Cohort Studies
- Disease Progression
- 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)
- White People
(genetics, statistics & numerical data)
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