TNF Block Gene Variants Associated with Pain Intensity in Black Southern Africans with HIV-associated Sensory Neuropathy
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Objectives: HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection, and often is painful. Tumour necrosis factor (TNF)-[alpha] 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 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. Methods: Single nucleotide polymorphisms (SNPs) defining TNF block haplotypes and African-specific tagSNPs were genotyped in samples from 150 black Southern Africans with HIV-SN. Results: One SNP allele, rs28445017*A, was significantly associated with increased pain intensity after correction for age, sex and CD4 T-cell count. A common 3-SNP haplotype containing rs28445017*G remained associated with reduced pain intensity after correction for covariates and multiple comparisons. Discussion: We identified a novel genetic associations between polymorphisms in the TNF block and 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 risk for HIV-SN as such, highlighting potential differences between the pathophysiology of the neuropathy and the painful features of the neuropathy. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Wadley, A.; Hendry, L.; Kamerman, P.; Chew, C.; Price, Patricia; Cherry, C.; Lombard, Z. (2015)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 ...
Wadley, A.; Cherry, C.; Price, Patricia; Kamerman, P. (2011)Context: HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of both HIV and neurotoxic antiretroviral medications such as stavudine. Objectives: To determine the prevalence, risk factors, and clinical ...
Goullee, H.; Wadley, A.; Cherry, C.; Allcock, R.; Black, M.; Kamerman, P.; Price, Patricia (2016)HIV-associated sensory neuropathy (HIV-SN) is the most common neurological condition associated with HIV. HIV-SN has characteristics of an inflammatory pathology caused by the virus itself and/or by antiretroviral treatment ...