Abstract
HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians and whites. Here we investigated genetic associations with HIV-SN in 342 black Southern Africans (190 cases and 152 neuropathy-free controls) using single nucleotide polymorphisms (SNPs) spanning the TNF block and a set of haplotypes defined by 31 SNPs in Asian and white populations (denoted FVa). We included population-appropriate tagSNPs derived from an African population (Yoruban, YRI, HapMap) and derived extended haplotypes comprising 61 SNPs (denoted FVa_ext b). We found no association between HIV-SN and carriage of two SNPs (TNF-1031/rs1799964*C and BAT1 (intron10)/rs9281523*C) associated with HIV-SN in whites and Asians. Additionally, a haplotype containing TNF-1031/rs1799964*C associated with increased risk of HIV-SN in Asians, but was not present in this African population. However, alleles of seven SNPs associated with reduced risk of HIV-SN (corrected for age, height and multiple comparisons). These were rs11796*A, rs3130059*G, rs2071594*C, NFKBIL1-62/rs2071592*A, rs2071591*A, LTA+252/rs909253*G, rs1041981*C. One haplotype (FV18_ext1), not containing these alleles, was associated with increased risk of HIV-SN after correction for age, height and multiple comparisons. Our results confirm the involvement of genes in the TNF block in altering risk for HIV-SN, but genotypes critical in this African population differed from those affecting HIV-SN in whites and Asians. These differences support the need for genetic association studies in diverse populations.
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Acknowledgements
We wish to thank the staff and the patients of the Virology Clinic in the Charlotte Maxeke Johannesburg Academic Hospital and Florence Mtsweni for acting as the interpreter for the study. In addition we would like to thank Punita Pitamber for her assistance with genotyping. We gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute (CLC) and the International Association for the Study of Pain for a Developed-Developing Countries Collaborative Research Grant (CLC, PRK). Finally we wish to thank the Belgian Technical Cooperation (LMH) and the Hillel Friedland Trust (ALW) for Fellowships. This work was directly supported by the University of the Witwatersrand, South Africa (Faculty of Health Sciences and the University Research Council) and the National Research Foundation, South Africa (Rated Researchers Program).
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Wadley, A., Hendry, L., Kamerman, P. et al. Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans. Eur J Hum Genet 23, 363–368 (2015). https://doi.org/10.1038/ejhg.2014.104
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DOI: https://doi.org/10.1038/ejhg.2014.104
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