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Haplotype diversity in the interleukin-4 gene is not associated with HIV-1 transmission and AIDS progression

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Abstract

Interleukin-4 (IL-4) is a pleiotropic cytokine produced primarily by activated CD4+ T lymphocytes, mast cells, and basophils. It modulates the functions of a variety of cell types involved with the immune response. This cytokine differentially regulates two major HIV-1 coreceptors and activates viral expression, and is thus a reasonable candidate gene for analyses in HIV-1/AIDS cohort studies. Population genetic variation in five single nucleotide polymorphisms (SNPs) in the 5′ region of the IL-4 gene was assessed in five racial groups. Neutrality tests reveal that the populations are evolving in accord with the infinite-sites model. However, coalescent simulations suggest greater haplotype diversity among African Americans than expected. This increased variation is presumably attributable to recombination or gene conversion. Genetic epidemiological analyses were conducted among European American and African American participants enrolled in five USA-based HIV-1/AIDS cohorts. One SNP, −589T, known to influence IL-4 transcription was previously shown to be associated with HIV-1/AIDS in both Japanese and French populations. Present analyses failed to identify any significant associations with HIV-1 infection or progression to AIDS.

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Acknowledgements

Michael Sanford, Julie Bergeron, Elizabeth Binns-Roemer, and Mary McNally provided laboratory expertise. James Lautenberger and George Nelson assisted with the analyses. William Klitz collected the Meso-American Amerindians samples. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-124000. All experiments were carried out with institutional IRB approval of the National Institutes of Health.

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  1. David Vlahov

    Present address: New York Academy of Medicine, 1216 5th Avenue, New York, NY 10029, USA

Authors and Affiliations

  1. Basic Research Program, SAIC Frederick, National Cancer Institute-FCRDC, Frederick, MD 21702-1201, USA

    William S. Modi & Cheryl Winkler

  2. Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA

    Thomas R. O'Brien

  3. Johns Hopkins School of Hygiene and Public Health for AIDS Link to the Intravenous Experience, Baltimore, MD 21205, USA

    David Vlahov

  4. San Francisco Department of Public Health, San Francisco, CA 94102, USA

    Susan Buchbinder

  5. Children's Hospital Los Angeles, Los Angeles, CA 90027, USA

    Edward Gomperts

  6. Department of Medicine, Northwestern University Medical School, Evanston, IL 60611, USA

    John Phair

  7. Laboratory of Genomic Diversity, National Cancer Institute-FCRDC, Frederick, MD 21702-1201, USA

    Stephen J. O'Brien

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Correspondence to Cheryl Winkler.

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Modi, W.S., O'Brien, T.R., Vlahov, D. et al. Haplotype diversity in the interleukin-4 gene is not associated with HIV-1 transmission and AIDS progression. Immunogenetics 55, 157–164 (2003). https://doi.org/10.1007/s00251-003-0541-5

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