RESUMO
INTRODUCTION: Animal and in vitro models of HIV-associated sensory neuropathy suggest an inflammatory etiology. Previous genetic association studies of HIV-SN have been in small Caucasian or Asian cohorts. We assessed cytokine single nucleotide polymorphisms (SNPs) in a Black Southern African cohort. METHOD: 342 black HIV-positive Southern Africans were recruited. 190 individuals had HIV-associated sensory neuropathy and 152 did not. DNA samples from all participants were genotyped for cytokine SNPs identified in studies of HIV disease and/or neuropathy. RESULTS: IL4-590*T associated with an increased prevalence of HIV-SN including following correction for age, height and CD4 T-cell count. No other cytokine SNPs assessed displayed an association. DISCUSSION: We identified a novel association between IL4-590*T and HIV-SN in African HIV-positive patients which warrants further investigation.
Assuntos
Infecções por HIV/genética , Infecções por HIV/imunologia , Interleucina-4/genética , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/imunologia , Polimorfismo de Nucleotídeo Único , População Negra/genética , Estudos de Coortes , Frequência do Gene , Estudos de Associação Genética , Infecções por HIV/epidemiologia , Humanos , Doenças do Sistema Nervoso Periférico/epidemiologia , Prevalência , África do SulRESUMO
Haplotypes spanning the tumor necrosis factor (TNF) gene block in the central major histocompatibility complex were defined in a Southern African population using 31 single-nucleotide polymorphisms. Twenty haplotypes accounted for 91.8% of the cohort. The haplotypes matched those described previously in Caucasian and Asian populations, supporting the hypothesis that TNF block haplotypes are ancient and highly conserved. They are presented here as a tool for disease-association studies.
Assuntos
População Negra/genética , Haplótipos , Fatores de Necrose Tumoral/genética , Povo Asiático/genética , Estudos de Casos e Controles , Humanos , Polimorfismo de Nucleotídeo Único , População/genética , África do Sul , População Branca/genéticaRESUMO
In human immunodeficiency virus (HIV) patients, neuropathy is a common adverse side effect to some antiretroviral treatments, particularly stavudine. As stavudine is cheap, it is widely used in Asia and Africa. We showed that increasing age and height moderately predict the development of neuropathy. This was improved by the inclusion of tumour necrosis factor (TNF)-1031 (rs1799964). To investigate this association, Malay (n = 64), Chinese (n = 74) and Caucasian patients (n = 37) exposed to stavudine were screened for neuropathy. DNA samples were genotyped for polymorphisms in the central major histocompatibility complex (MHC) near TNF, and haplotypes were derived. The haplotype group FVa6,7,8 (incorporating TNF-1031) was found to be associated with neuropathy in Chinese patients in bivariate analyses (P = 0.03), and in Malays and Chinese in a multivariate analysis correcting for age and height (P = 0.02, P = 0.03, respectively). This trend was also confirmed in Caucasians.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Haplótipos/genética , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Polimorfismo Genético/genética , Estavudina/efeitos adversos , Fatores de Necrose Tumoral/genética , Antropometria , Povo Asiático/genética , Estatura , Genótipo , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Infecções por HIV/patologia , Humanos , Reação em Cadeia da Polimerase , Medição de Risco , Fatores de Risco , População Branca/genéticaRESUMO
The region spanning the tumour necrosis factor (TNF) cluster in the human major histocompatibility complex is implicated in susceptibility to immunopathological disease, but ethnic differences and linkage disequilibrium have hampered identification of critical polymorphisms. Here, we investigate Europeans, Asians (Bidayuh, Chinese, Indian, Jehai, Malay, Temuan) and Australian Aborigines to provide a framework for disease-association studies. DNA from 999 unrelated healthy donors was genotyped at 38 loci, primarily in coding and promoter regions over a 60-kb region spanning seven genes near TNF. The PHASE algorithm was used to statistically infer TNF block haplotypes and estimate their frequencies in each population. The TNF block is carried as 31 haplotypes in all populations combined, with <19 in any single population. Only six haplotypes have a unique tag single nucleotide polymorphism (SNP) valid for all populations, but seven haplotypes could be tagged with individual SNPs in selected populations. Four to eight TNF block haplotypes exist across all ethnicities, and hence must pre-date the divergence of these populations from a common ancestor >160,000 years ago. Some haplotypes are unique to isolated populations, but they do not contain unique SNP. Hence, they reflect restricted migration and/or extinction of some families rather than de novo mutation.
