哈尔滨市HIV-1感染者TRIM5α基因多态性与艾滋病的相关性

Correlations between TRIM5α gene polymorphisms and acquired immune dificiency syndrome of HIV-1infected patients in Harbin

目的分析编码TRIM5α蛋白的基因2号外显子单核苷酸基因多态性（single nucleotide polymorphisms，SNPs）与艾滋病的相关性，并探讨病毒亚型对此相关性的影响。方法从331例已确诊但未接受治疗的HIV-1感染者的外周血单个核细胞（peripheral blood mononuclear cell，PBMC）中提取基因组DNA，扩增HIV-1病毒的Gag基因和编码TRIM5α蛋白基因的2号外显子基因并获得基因序列信息，统计单核苷酸多态性（single nucleotide polymorphisms，SNPs）和构建Gag基因系统进化树图。以CD4＋T淋巴细胞数200个/μL为界值将HIV-1感染者分为快速进展组（CD4〈200）和慢速进展组（CD4≥200），并分析比较所有331例样本和各HIV-1亚型中TRIM5α基因多态性与艾滋病的相关性。结果在全部扩增的331条HIV-1的Gag基因中，有239条Gag基因序列与不同的CRF01_AE亚簇聚集，CRF01_AE亚型感染者占所有感染者的72.2%，其他亚型较少，故不进行相关性分析。我们共发现4个SNP位点（-2GC、127CT、334GT和407GA），其中407GG基因型在所有样本和CRF01_AE感染者的快速进展组和慢速进展组中都有明显的统计学差异（P〈0.05），而407GA基因型只在CRF01_AE感染者中有统计学差异。结论突变位点-2G/C、127C/T、334G/T和HIV-1的感染无相关性，407G/A突变可能与宿主TRIM5α蛋白抗HIV-1的作用增强相关，而HIV-1病毒型别是研究TRIM5α基因多态性和艾滋病相关性应该考虑的因素。

ObjectiveTo analyze the correlation between the single nucleotide polymorphisms（SNPs） of exon2 in TRIM5α gene and acquired immune dificiency syndrome（AIDS）. The effect of the virus subtype on this correlation was also discussed.MethodsThe genomic DNA was extracted from peripheral blood mononuclear cells of 331 patients with well established？ HIV-1 infection but untreated.The gag gene of HIV-1 and the exon2 in TRIM5α were amplified and sequenced.The SNPs and the phylogenetic tree were constructed.The patients were divided into two groups according to the numbers of CD4 cells： fast progression group （CD4〈200） and slow progression group（CD4≥200）. SNPs were calculated and the correlation between TRIM5α gene polymorphism and AIDS was analyzed.Results239 strains of gag gene were clustered with different CRF01_AE subgroups.Infectors of CRF01_AE subtypes were the majority of all infected individuals（72.2%）. Other subtypes are less independent of correlation analysis.Four mutations in exon2 of the TRIM5α （-2GC, 127CT, 334GT, 407GA） were found.The difference of 407GG between high CD4 group and low CD4 group in infectors of CRF01_AE subtypes has statistical sense and it is the same in all infected （P〈0.05）. The genotypic composition of 407GA was only statistically different in infectors of CRF01_AE subtypes.ConclusionMutations on -2G/C, 127C/T and 334G/T have not been involved in TRIM5α gene polymorphism and AIDS.Mutations on 407G/A may be associated with the enhancement of the role of the host TRIM5α protein against HIV-1.In addition, the HIV-1 subtype is a factor that should be considered for the correlation of TRIM5α gene polymorphism and AIDS.