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/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, 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.
From the *Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL; †Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; ‡Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL; §Children’s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania, Philadelphia, PA; ||Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany; and ¶Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
Received for publication August 29, 2003; accepted December 9, 2003.
Supported by grants AI41951, AI51173, DA04347, and HD32842 from the National Institutes of Health. The REACH study was funded by grant U01 HD32830 from the National Institute of Child Health and Human Development, with additional funding from the National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, and National Institute of Mental Health.
Data derived from this work were presented in part as abstract 256 [Hum Immunol. 2003;64(Suppl):S173] at the 29th Annual Meeting of the American Society for Histocompatibility and Immunogenetics, Miami Beach, FL, October 28–November 1, 2003.
Reprints: Richard A. Kaslow or Jianming Tang, Program in Epidemiology of Infection and Immunity, School of Public Health, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294–0022 (e-mail: email@example.com or firstname.lastname@example.org).