中国北方人群HIV-1感染及AIDS进展与病毒限制因子基因多态性的相关性研究

Our understanding of the early events in HIV-1 infection continues to grow, along with the heightened recognition of the important contribution that innate immunity plays in response to HIV-1. A growing number of genomic studies have described polymorphisms in innate immune genes those are associated with early postseroconversion events. TRIM5a and APOBEC3 play a crucial role in the primate antiviral defense system. Several studies have systematically investigated the role of polymorphisms in TRIM5a and APOBEC3 and susceptibility to HIV acquisition or progression in Caucasian populations, and the results are encouraging. However, the association between these functional polymorphisms and HIV acquisition or progression is still unknown in the North Chinese populations and requires further investigations. A total of 1600 individuals, comprising 800 HIV-1 infected persons and 800 healthy controls, will be included in this large case-control study. Firstly, we will analyze the sequences of TRIM5a, APOBEC3G and APOBEC3H by resequencing the genes in 45 HIV-1 infected persons and 15 healthy controls. Secondly, we will determine the distribution of each polymorphism in 800 HIV-1 infected persons and 800 healthy controls, and examine the association of the polymorphisms and their interactions with HIV acquisition or progression. This study might provide new insights to further elucidate the pathogenesis of AIDS. This would also provide scientific basis in screening and prevention of high-risk groups of HIV acquisition or progression and improve patient outcomes.

病毒限制因子在机体抵御HIV-1感染过程中发挥着重要功能，其中TRIM5α及APOBEC3对HIV-1的限制作用尤为关键。研究表明，TRIM5α、APOBEC3基因多态性可能与人类HIV-1感染和AIDS疾病进程相关，然而此类关联研究主要集中在欧美人群，目前尚无有关中国北方人群的报道。本课题拟利用分子生物学和生物信息学的方法，从单个位点、单倍型、多位点联合作用、基因-环境交互作用分析等几个方面，探讨病毒限制因子TRIM5α、APOBEC3基因多态性与中国北方人群HIV-1感染及AIDS发生的相关性，探讨基因多态性与AIDS不同进展阶段之间的关系。本研究将为揭示中国北方人群HIV-1感染的分子生物学机制，制定AIDS防治策略提供新的思路。

本项目以北方汉族485例男性同性恋HIV-1感染者和493例男性对照个体为样本，采用SNPscan分析方法，分别对TRIM5α基因rs7127617、rs10838534、rs10734538、rs57197373、rs3802981、rs3802980、rs3824949、rs3740996、rs10838525、rs11038628、rs55723753、rs1976339、rs77628708、rs12272771、rs7127767、rs7116587、rs2880575、rs7124435、rs17305868；TRIM22基因rs1063303、rs7935564、rs10838543，APOBEC3H基因rs139294、rs139297、rs139298 、rs139302多态位点进行基因分型。采用SPSS17.0软件进行统计分析，统计TRIM5α、TRIM22、APOBEC3H各多态位点的不同等位基因在HIV-1感染者和对照组中的分布，比较HIV-1感染者与对照组组间基因型和等位基因频率的差异，阐明各多态位点与北方汉族人群男性同性恋HIV-1感染的关系。研究发现，TRIM5α基因rs3740996（H43Y）位点、rs10838525（R136Q）位点等位基因与男性同性恋HIV-1感染发生存在关联（rs3740996，OR=1.40，95% CI 1.11-1.73，P=0.005；rs10838525，OR=1.65，95% CI 1.05-2.63，P=0.033）；TRIM22基因rs1063303、rs7935564位点等位基因与男性同性恋HIV-1感染发生存在关联（rs1063303，OR=1.44，95% CI 1.11-1.88，P=0.009；rs7935564，OR=1.38，95% CI 1.10-1.71，P=0.010）；APOBEC3H基因rs139298位点等位基因与男性同性恋HIV-1感染发生存在关联（OR=1.26，95% CI 1.05-1.54，P=0.022）。其余基因位点与中国北方汉族人群男性同性恋HIV-1感染发生不存在显著关联（P>0.05）。本研究将为揭示中国北方人群男性同性恋HIV-1感染的分子生物学机制，制定AIDS防治策略提供新的思路。本项目已顺利完成，目前1篇英文文章待发表。