title: Cytokine and chemokine gene polymorphisms among ethnically diverse North Americans with HIV-1 infection.
abstract: Twenty-four common single nucleotide polymorphisms (SNPs) in 10 cytokine and chemokine genes were defined in 579 North Americans at high risk of HIV-1 infection due to sexual behavior and injection drug use. Among the 3 major ethnic (African-American, Hispanic/Latino, and other) groups involved, HIV-1-seropositive individuals differed significantly from ethnically matched HIV-1-seronegative individuals (odds ratios = 2.13-4.82; P = 0.003-0.05) for several SNPs and haplotypes defined at the IL4, IL4R, IL6, IL10, CCL5 (RANTES), and CXCL12 (SDF1) loci. In addition, the homozygous IL4-590T/T genotype was associated with higher (+87-131 cells/microL) CD4 T-cell counts in HIV-1-infected and AIDS-free adolescents not receiving antiretroviral therapy (adjusted P = 0.004). No SNPs at IFNG, IL2, IL12B, TNF, or CCL2 (MCP1) showed any association with HIV-related outcomes. Additional typing for IL1A, IL1B, IL1R1, IL1RN, and TGFB1 SNPs also failed to demonstrate any influence on HIV-1 infection or virologic/immunologic control in more selected patient groups. Coupled with previous findings, our data suggest that heritable IL4 and IL10 variations may contribute to the acquisition or progression of HIV infection and that the effects of other targeted loci in the cytokine and chemokine system cannot be established unequivocally in the study populations.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Chengbin
authors.initials: C
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Elena
authors.initials: E
authors.lastname: Lobashevsky
authors.forename: Craig M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
authors.forename: Joannis
authors.initials: J
authors.lastname: Mytilineos
authors.forename: Ellie E
authors.initials: EE
authors.lastname: Schoenbaum
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D018925:Chemokines / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000208:ethnology / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D017058:Mexican Americans / Q000235:genetics; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic
chemical_list: D018925:Chemokines; D016207:Cytokines