title: Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans.
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.
authors.affiliation: Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Antonia L
authors.initials: AL
authors.lastname: Wadley
authors.affiliation: 1] Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa [2] Division of Human Genetics, School of Pathology, Faculty of Health Sciences, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Liesl M
authors.initials: LM
authors.lastname: Hendry
authors.affiliation: Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kamerman
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Constance S N
authors.initials: CS
authors.lastname: Chew
authors.affiliation: 1] Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa [2] School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
authors.affiliation: 1] Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa [2] International Clinical Research Laboratory, Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia [3] Infectious Diseases Unit, Alfred Hospital; and Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Cherry
authors.affiliation: 1] School of Molecular & Cell Biology, Faculty of Science, University of the Witwatersrand, Johannesburg, South Africa [2] Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Zané
authors.initials: Z
authors.lastname: Lombard
mesh_terms: D000328:Adult; D000483:Alleles; D044383:Black People; D002896:Chromosomes, Human, Pair 6; D005260:Female; D056426:Genetic Loci; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010523:Peripheral Nervous System Diseases / Q000209:etiology*; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha