The −1030/−862-linked TNF promoter single-nucleotide polymorphisms are associated with the inability to control HIV-1 viremia
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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.
This work was supported by grants from the NIH (HL-59838 to A.E.G), (AI-28568 to B.D.W), and (HL-67471 to J.C.D.) and from the American Heart Association to A.E.G. We thank Eric Rosenberg, Spyros Kalams, Stephen Boswell and James Braun for providing valuable samples.
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