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首页> 外文期刊>JAIDS: Journal of acquired immune deficiency syndromes >The major histocompatibility complex conserved extended haplotype 8.1 in AIDS-related non-Hodgkin lymphoma.
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The major histocompatibility complex conserved extended haplotype 8.1 in AIDS-related non-Hodgkin lymphoma.

机译：主要的组织相容性复合体在艾滋病相关的非霍奇金淋巴瘤中保留了扩展的单倍型8.1。

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BACKGROUND: Two single nucleotide polymorphisms (SNPs) in adjacent genes, lymphotoxin alpha (LTA +252G, rs909253 A>G) and tumor necrosis factor (TNF -308A, rs1800629 G>A), form the G-A haplotype repeatedly associated with increased risk of non-Hodgkin lymphoma (NHL) in individuals uninfected with HIV-1. This association has been observed alone or in combination with human leukocyte antigens HLA-B*08 or HLA-DRB1*03 in the major histocompatibility complex (MHC). Which gene variant on this highly conserved extended haplotype (CEH 8.1) in whites most likely represents a true etiologic factor remains uncertain. OBJECTIVE: We aimed to determine whether the reported association of the G-A haplotype of LTA-TNF with non-AIDS NHL also occurs with AIDS-related NHL. METHODS: SNPs in LTA and TNF and in 6 other genes nearby were typed in 140 non-Hispanic European American pairs of AIDS-NHL cases and matched controls selected from HIV-infected men in the Multicenter AIDS Cohort Study. RESULTS: The G-A haplotype and a 4-SNP haplotype in the neighboring gene cluster (rs537160 (A) rs1270942 (G), rs2072633 (A), and rs6467 (C)) were associated with AIDS-NHL (odds ratio = 2.7, 95% confidence interval: 1.5 to 4.8, P = 0.0009; and odds ratio = 3.2, 95% confidence interval: 1.6 to 6.6, P = 0.0008; respectively). These 2 haplotypes occur in strong linkage disequilibrium with each other on CEH 8.1. CONCLUSION: The CEH 8.1-specific haplotype association of MHC class III variants with AIDS-NHL closely resembles that observed for non-AIDS NHL. Corroboration of an MHC determinant of AIDS and non-AIDS NHL alike would imply an important pathogenetic mechanism common to both.
机译：背景：相邻基因中的两个单核苷酸多态性（SNP），淋巴毒素α（LTA + 252G，rs909253 A> G）和肿瘤坏死因子（TNF -308A，rs1800629 G> A）形成了GA单倍型，反复增加了罹患GA的风险未感染HIV-1的非霍奇金淋巴瘤（NHL）患者。已经在主要组织相容性复合物（MHC）中单独或与人类白细胞抗原HLA-B * 08或HLA-DRB1 * 03结合观察到这种关联。在白人中，这种高度保守的延伸单倍型（CEH 8.1）上的哪个基因变异最有可能代表真正的病因。目的：我们旨在确定所报道的LTA-TNF G-A单倍型与非AIDS NHL的关联是否也与AIDS相关NHL有关。方法：在多中心艾滋病队列研究中，在140例非西班牙裔欧洲裔美国人AIDS-NHL病例中选择了LTA和TNF以及附近的其他6个基因中的SNP，并从HIV感染男性中选出了匹配的对照。结果：邻近基因簇（rs537160（A）rs1270942（G），rs2072633（A）和rs6467（C））中的GA单倍型和4-SNP单倍型与AIDS-NHL相关（优势比= 2.7、95） ％置信区间：1.5至4.8，P = 0.0009;比值比= 3.2，95％置信区间：1.6至6.6，P = 0.0008;）。在CEH 8.1上，这2个单倍型彼此之间存在强烈的连锁不平衡。结论：MHC III类变体与AIDS-NHL的CEH 8.1特异性单倍型关联与非AIDS NHL的相似。确证艾滋病和非艾滋病人非霍奇金淋巴瘤的MHC决定因素将暗示两者共同的重要发病机制。

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