• Liesl M Hendry, Antonia L Wadley, Catherine L Cherry, Patricia Price, Zané Lombard, and Peter R Kamerman.
• *Brain Function Research Group, School of Physiology, Faculty of Health Sciences †Division of Human Genetics, School of Pathology, Faculty of Health Sciences and National Health Laboratory Service ¶School of Molecular & Cell Biology, Faculty of Science #Division of Bioinformatics, Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa ‡International Clinical Research Laboratory, Centre for Biomedical Research, Burnet Institute §Infectious Diseases Unit, Alfred Hospital and Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic. ∥School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia.
• Clin J Pain. 2016 Jan 1; 32 (1): 455045-50.

ObjectivesHIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection, and it is often painful. Tumor necrosis factor (TNF)-α is implicated in neuropathic pain, but associations between neuropathic pain and polymorphisms in the TNFA gene have not been identified. The "TNF block" is a region of high linkage disequilibrium within the central major histocompatability complex that contains several genes involved in the regulation of inflammation, including TNFA. Polymorphisms in the block have been associated with an altered risk of HIV-SN, but no investigations into whether this region is associated with the painful symptoms of neuropathy have been undertaken. Therefore, we investigated whether polymorphisms in the TNF block are associated with pain intensity in black Southern Africans with HIV-SN.MethodsSingle-nucleotide polymorphisms (SNPs) defining TNF block haplotypes and African-specific tagSNPs were genotyped in samples from 150 black Southern Africans with HIV-SN.ResultsOne SNP allele, rs28445017*A, was significantly associated with an increased pain intensity after correction for age, sex, and the CD4 T-cell count. A common 3-SNP haplotype containing rs28445017*G remained associated with a reduced pain intensity after correction for covariates and multiple comparisons.DiscussionWe identified a novel genetic association between polymorphisms in the TNF block and the pain intensity in black Southern Africans with HIV-SN. Our study implicates rs28445017 in painful HIV-SN, although its precise role and whether it may be causative is unclear. rs28445017 was not associated with the risk for HIV-SN as such, highlighting potential differences between the pathophysiology of the neuropathy and the painful features of the neuropathy.

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