Analysis of a biallelic polymorphism in the tumor necrosis factor a promoter and HIV type 1 disease progression
Analysis of a biallelic polymorphism in the tumor necrosis factor a promoter and HIV type 1 disease progression
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DOI：
10.1089/aid.1998.14.305
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发表时间：
1998-03-01
影响因子：
1.5
通讯作者：
Lal, RB
中科院分区：
文献类型：
--
作者：
Knuchel, MC;Spira, TJ;Lal, RB
研究人员检测了tnf - α启动子多态性（位于308位的G-to-A多态性序列）的相关性，以检测tnf - α变异等位基因是否影响HIV-1感染的易感性和艾滋病的进展。对HIV-1阳性男同性恋群体标本的分析表明，32名HIV-1感染长期非进展者（LTNPs）中有3名（9.4%）是罕见的TNF-2等位基因的纯合子，而196名HIV-1血清阴性献血者和未感染的男同性恋者中有3名（1.5%）是纯合子（p < 0.05）， HIV-1血清阳性组和-血清阴性组之间的杂合子性无差异。尽管一些血清阳性男性的TNF2基因型杂合也为CCR5 δ 32杂合。然而，当分析来自芝加哥MACS的血清事件（n = 109）和血清价病例（n = 442）时，TNF基因型与生存时间、CD4斜坡或病毒载量之间没有显著关联。血清阴性组淋巴细胞的功能分析显示，不同TNF基因型供者在内源性或丝裂原诱导的TNF- α产生以及体外HIV-1感染的易感性方面没有差异。这些数据表明TNF基因型在HIV-1疾病进展中不起直接作用；然而，它们可能是多基因联系的一部分，可能涉及延缓艾滋病的进展。
The relevance of a TNF-alpha promoter polymorphism, a G-to-A polymorphic sequence at position-308, was examined to test whether variant alleles of TNF-alpha affect susceptibility to infection with HIV-1 and progression to AIDS. Analysis of specimens from cohorts of HIV-1 positive homosexual men demonstrated that 3 of the 32 (9.4%) HIV-1-infected long-term nonprogressors (LTNPs) were homozygous for the uncommon TNF-2 allele compared with 3 of the 196 (1.5%) HIV-1-seronegative blood donors and uninfected homosexual men (p < 0.05), There was no difference in heterozygosity among HIV-1-seropositive or -seronegative groups, although some of the seropositive men heterozygous for the TNF2 genotype were also heterozygous for CCR5 Delta 32. However, no significant association was found between TNF genotypes and time of survival, CD4 slopes, or viral loads when seroincident (n = 109) and seroprevalent cases (n = 442) from the Chicago MACS were analyzed, Functional analysis of lymphocytes from the seronegative group revealed no difference in endogenous or mitogen-induced TNF-alpha production, as well as susceptibility to in vitro HIV-1 infection between different TNF-genotype donors, These data suggest that TNF genotypes do not play a direct role in HIV-1 disease progression; however, they could potentially be part of a multigenic linkage that may be involved in delaying progression to AIDS.