TNF-alpha promoter region gene polymorphisms in HIV-positive patients with lipodystrophy

The pathogenic mechanisms underlying lipodystrophy in HIV-positive patients are largely unknown. TNF-alpha has many actions that are consistent with the features of lipodystrophy; therefore, an analysis was carried out to determine whether functionally active polymorphisms in the promoter region of the TNF-alpha gene are associated with the development of lipodystrophy.

Genetic case-control association study.

Individuals were genotyped for the -238 and -308 polymorphisms in the TNF-alpha gene using polymerase chain reaction-restriction fragment length polymorphism analysis. The genotype and allele frequencies for 61 HIV-positive patients with lipodystrophy were compared with (a) 35 HIV-positive patients with no evidence of lipodystrophy and (b) 239 healthy HIV-negative individuals.

The frequency of the variant rare -238 allele was significantly different (P = 0.01) in HIV-positive patients with lipodystrophy than in those without lipodystrophy. At the genotype level, a trend towards a difference between patients with and without lipodystrophy was observed (chi2 for linear trend 5.2, P = 0.02). For the -308 polymorphism, no difference was found in genotype and allele frequencies between HIV patients with and without lipodystrophy.

The data suggest that the -238 (but not the -308) promoter region TNF-alpha gene polymorphism is a determinant in the development of HIV-related lipodystrophy. However, the results need to be confirmed in larger numbers of patients as well as in an ethnically diverse population.