Control of HIV-1 viremia and progression to AIDS has been associated with specific HLA genes. The tumor necrosis factor (TNF) and the non-classical major histocompatibility (MHC) class I chain-related A (MICA) genes are located in the genomic segment between the HLA class I and II genes and variants of both genes have been identified. We thus analyzed TNF promoter and MICA variants in a well-characterized group of HIV-1 infected individuals with different abilities to control HIV-1 viremia. In our cohort, the -1030/-862-linked TNF promoter single-nucleotide polymorphisms (SNPs), but not MICA variants, are significantly associated with lack of control of HIV-1 viremia (P=0.03). This association is independent of those HLA-B35 alleles associated with HIV-1 disease progression with which the -862 TNF SNP has previously been independently associated. Thus, non-randomly associated genes near the TNF locus are likely involved in control of HIV-1 viremia.
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