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Association of Toll-like receptor polymorphisms with HIV status in North Americans

Genes & Immunity volume 15, pages 569–577 (2014)Cite this article

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Abstract

Single-nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes TLR2– 4 and TLR7– 9, but not in TLR1 and TLR6, have been previously evaluated regarding human immunodeficiency virus (HIV) acquisition and disease progression in various populations, most of which were European. In this study, we examined associations between a total of 41 SNPs in 8 TLR genes (TLR1–4, TLR6–9) and HIV status in North American subjects (total n=276 (Caucasian, n=102; African American, n=150; other, n=24)). Stratification of the data by self-identified race revealed that a total of nine SNPs in TLR1, TLR4, TLR6 and TLR8 in Caucasians, and two other SNPs, one each in TLR4 and TLR8, in African Americans were significantly associated with HIV status at P<0.05. Concordant with the odds ratios of these SNPs, significant differences were observed in the SNP allele frequencies between HIV+ and HIV− subjects. Finally, in Caucasians, certain haplotypes of single (TLR1 and TLR4) and heterodimer (TLR2_TLR6) genes may be inferred as ‘susceptible’ or ‘protective’. Our study provides in-depth insight into the associations between TLR variants, particularly TLR1 and TLR6, and HIV status in North Americans, and suggests that these associations may be race specific.

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Acknowledgements

This study was supported by grants from the National Institute of Dental and Craniofacial Research (1P01DE019759, AW; Project 4, RJJ and PAZ), Fogarty International Center (D43TW007377, support for BW) and National Heart Lung and Blood Institutes (T32HL007567, support for NBH) at the National Institutes of Health. We are indebted to Drs Michael Lederman and Benigno Rodriguez for providing the HIV-infected patient samples from the CFAR specimen repository. We are thankful to Simone Edelheit and Milena Rajak (Genomics Core Facility) for performing the TLR SNP genotyping, and to Melinda Zikursh for performing the Duffy genotyping. We sincerely thank Dr Daniel Tisch, Dave McNamara, Dr Scott Sieg and Ramalakshmi Janamanchi for helpful discussions and critical evaluation of the manuscript.

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  1. R J Jurevic

    Present address: 6Current address: Department of Oral Diagnostics, School of Dentistry, West Virginia University, Morgantown, WV, USA.,

  2. B Willie and N B Hall: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    B Willie, R K Mehlotra & P A Zimmerman

  2. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA

    N B Hall & C M Stein

  3. Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    C M Stein

  4. Department of Biological Sciences, Case Western Reserve University School of Dental Medicine, Cleveland, OH, USA

    R J Jurevic & A Weinberg

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Willie, B., Hall, N., Stein, C. et al. Association of Toll-like receptor polymorphisms with HIV status in North Americans. Genes Immun 15, 569–577 (2014). https://doi.org/10.1038/gene.2014.54

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