2011年4月6日星期三

【China AIDS:6409】 JAIDS:中国静脉吸毒人群TRIM5α基因多态性与HIV-1易感性的关系研究取得进展

在生物的整个进化过程中,生物体进化出了各种"武器"来对抗各种病毒的入侵。为了对付HIV-1的感染,灵长类针对HIV-1在细胞内的复制过程产生了各种抑制HIV-1病毒复制的限制因子,如三模体蛋白5α(TRIM5α)、载脂蛋白B mRNA编辑酶3G(APOBEC3G)、束缚蛋白(tetherin) 和锌指结构抗病毒蛋白(ZAP)等。限制因子的基因多态性往往与个体对病毒易感性和感染后病程进展的差异密切相关。人TRIM5α的基因多态性与HIV-1易感性及病程进展相关性研究所得到的结论并不一致,而且缺乏中国规模人群TRIM5α多态性的研究。

中国科学院昆明动物研究所动物模型与人类疾病机理重点实验室博士生刘丰亮等人在导师郑永唐研究员及香港中文大学邓亮生教授的指导下,对云南省的1294名汉族或傣族静脉吸毒者的TRIM5α的基因多态性与HIV-1易感性的相关性进行研究。研究共发现14个基因变异,除之前已有报道的-2G/C、H43Y、V112F、R136Q等几个重要的SNP位点之外,还新发现了I2V、R97C、G110R等罕见的突变位点。对4个基因频率较高的SNP(即常见SNP)进行相关性分析,结果发现-2G/C、V112F和R136Q这3个SNP的基因型频率和基因频率以及4个常见SNP的单倍体在HIV-1阳性群体和阴性群体中的分布没有统计学差异,而H43Y的纯合突变基因型(TT)在静脉吸毒HIV-1感染者中频率显著低于静脉吸毒HIV-1未感染者,并且这种统计学差异在对数据进行民族方面的分层分析后仍然存在,这就提示H43Y在中国静脉吸毒者中极有可能起保护作用。研究成果近期已发表在国际著名的艾滋病学术期刊JAIDS (56:306-311, 2011)上。

该研究得到了973项目、NSFC-云南联合基金、国家重大科技专项、中国科学院等项目资助和云南省疾病预防控制中心的协助。(生物谷Bioon.com)

生物谷推荐相关文章:

Journal of Acquired Immune Deficiency Syndromes   doi: 10.1097/QAI.0b013e318205a59b

An HIV-1 Resistance Polymorphism in TRIM5α Gene Among Chinese Intravenous Drug Users

Liu, Feng-Liang MS*??; Qiu, Yu-Qing PhD§; Li, Hong MS‖; Kuang, Yi-Qun PhD*??; Tang, Xia MS*??; Cao, Guang BS*??; Sang Tang, Nelson Leung MD?§?; Zheng, Yong-Tang PhD*?

Background: TRIM5α has species-specific restriction activity against replication of many retroviruses, including HIV-1. Though human also express TRIM5α protein, it is less potent in suppressing infection of HIV-1 than most orthologs of other nonhuman primates. Previous association studies suggested that polymorphisms in TRIM5α gene might protect against HIV-1 infection. However, the exact variation accounting for this protective effect was not certain.

Methods: One thousand two hundred ninety-four Chinese intravenous drug users (IDUs), including 1011 Hans and 283 Dai subjects, were investigated for sequence variations in TRIM5α and association with HIV-1 resistance. Resequencing of the putative functional domains in exon2 and exon8 was carried out in 1151 subjects, along with exon2 resequencing in a further 143 HIV-1-infected IDUs.

Results: We identified 14 different nucleotide variants, including 4 with minor allele frequency >0.05. We observed that the frequency of 43Y homozygote in seronegative IDUs was significantly higher than that in the HIV-1-infected IDUs, suggesting a protective effect among the homozygote subjects [odds ratio (95% confidence interval) = 0.46 (0.22 to 0.94), P = 0.033, Mantel-Haenszel test].

Conclusions: we concluded that H43Y might account for the HIV-1 resistance due to TRIM5α gene in Chinese IDUs.

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