摘要
Objective To evaluate the frequencies and polymorphisms of CCR5-△32,CCR2-641 and SDF1-3'A alleles conferring resistance to HIV-1 infection in Chinese population from Han ethnic origin.Methods This cohort was comprised of 1251 subjects(915 men and 336 women)aged 15 -80 years and none was HIV-1 positive.Genotyping of allelic CCR5-△32,CCR2-641 and SDF1-3' A variants was performed using PCR or PCR/RFLP assay,and further confirmed by direct DNA sequencing.Results Our finding shows that the△32 deletion mutation in the CCR5 gene does occur in this population and can be inherited in a Mendelian fashion in indigenous Han Chinese at a very low frequency of 0.00119(n= 1254).The frequencies of mutant CCR2-641 and SDF1-3'A alleles were 0.20023(n = 1251)and 0.2873(n = 893),in this population,which are higher than those found in American Caucasians.Furthermore the polymorphisms of CCR2-641 and SDF1-3' A alleles in the Han Chinese population were different from those in American Caucasians.Statistical analysis showed that the genotype distribution of CCR5-△32,CCR2-641 and SDF1-3' A alleles was in equilibrium according to the Hardy-Weinberg equation.Conclusion The CCR5-△32 mutation may not be a major resistant factor against HIV-1 infection in indigenous Han Chinese.The significance of higher frequencies of CCR2-641 and SDF1-3' A alleles (0.20023 and 0.2791)in the Han population remains to be clarified in HIV-1-positive carriers and AIDS patients.
目的 为了评估中国汉族人群对HIV感染的遗传易感性 ,我们检测和分析了相应人群的CCR5 △ 32、CCR2 6 4I和SDF1 3’A等位基因的突变频率和多态性。方法 被研究的人群包括 12 5 4例中国普通汉族人 (918例男性、336例女性 ) ,年龄范围在 15 - 80岁之间 ,他们中没有HIV感染者。应用PCR和PCR/RFLP等分子生物学方法检测了CCR5 △ 32、CCR2 6 4I和SDF1 3’A等位基因型 ,用直接DNA测序法进一步证实其准确性。结果 我们发现在汉族人的CCR5基因编码中的确存在△ 32碱基缺失突变 (频率为 0 0 0 119,n =12 5 4) ,并可能经过孟德尔方式遗传 ;而CCR2 6 4I和SDF1 3’A等位基因的突变频率分别是 0 2 0 0 2 3(n =12 5 1)和 0 2 873(n =893)。可见汉族人群的CCR2 6 4I和SDF1 3’A突变频率高于美国白人 ,并且在基因多态性组成上与美国白人不同。统计学分析表明中国汉族人群中上述三个等位基因型的分布符合Hardy Weinberg平衡。结论 上述结果提示中国汉族人群中CCR5 △ 32遗传突变可能不是抗HIV感染的主要因素 ,因此汉族人群对性传播的R 5病毒株可能有较大的遗传易感性。中国汉族人群具有较高的CCR2 6 4I和SDF1
基金
ThisprojectwassupportedbyagrantfromNationalNaturalSciencesFoundationofthePRChina (No 3 9770 683 )
