title: TNF Block Gene Variants Associate With Pain Intensity in Black Southern Africans With HIV-associated Sensory Neuropathy.
abstract: OBJECTIVE
  HIV-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.
  
  
  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 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: *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.
authors.forename: Liesl M
authors.initials: LM
authors.lastname: Hendry
authors.forename: Antonia L
authors.initials: AL
authors.lastname: Wadley
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Cherry
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
authors.forename: Zané
authors.initials: Z
authors.lastname: Lombard
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kamerman
mesh_terms: D000328:Adult; D044383:Black People; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006239:Haplotypes; D006801:Humans; D008297:Male; D010146:Pain / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D013019:South Africa; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha