TY - JOUR
T1 - Cytokine and Chemokine Gene Polymorphisms among Ethnically Diverse North Americans with HIV-1 Infection
AU - Wang, Chengbin
AU - Song, Wei
AU - Lobashevsky, Elena
AU - Wilson, Craig M.
AU - Douglas, Steven D.
AU - Mytilineos, Joannis
AU - Schoenbaum, Ellie E.
AU - Tang, Jianming
AU - Kaslow, Richard A.
PY - 2004/4/15
Y1 - 2004/4/15
N2 - 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, ILIO, CCL5 (RANTES), and CXCLI2 (SDFI) loci. In addition, the homozygous IL4-590T/T genotype was associated with higher (+87-131 cells/μL) 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, ILI2B, TNF, or CCL2 (MCP1) showed any association with HIV-related outcomes. Additional typing for IL1A, IL1B, IL1R1, IL1RN, and TGFBI 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.
AB - 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, ILIO, CCL5 (RANTES), and CXCLI2 (SDFI) loci. In addition, the homozygous IL4-590T/T genotype was associated with higher (+87-131 cells/μL) 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, ILI2B, TNF, or CCL2 (MCP1) showed any association with HIV-related outcomes. Additional typing for IL1A, IL1B, IL1R1, IL1RN, and TGFBI 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.
KW - Allele
KW - Chemokine
KW - Cytokine
KW - Genetics
KW - HIV-1
KW - Infection
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U2 - 10.1097/00126334-200404150-00002
DO - 10.1097/00126334-200404150-00002
M3 - Article
C2 - 15021309
AN - SCOPUS:1842615034
SN - 1525-4135
VL - 35
SP - 446
EP - 454
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 5
ER -