title: 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.
authors.affiliation: SAIC Frederick, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Modi
authors.forename: K
authors.initials: K
authors.lastname: Scott
authors.forename: J J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: D
authors.initials: D
authors.lastname: Vlahov
authors.forename: S
authors.initials: S
authors.lastname: Buchbinder
authors.forename: R
authors.initials: R
authors.lastname: Detels
authors.forename: S
authors.initials: S
authors.lastname: Donfield
authors.forename: S J
authors.initials: SJ
authors.lastname: O'brien
authors.forename: C
authors.initials: C
authors.lastname: Winkler
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000706:statistics & numerical data; D000483:Alleles; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC