香港特区中国人群HIV辅助受体CCR5开放读码区天然突变的研究

目的研究中国人群CCR5基因开放读码区(open reading frame,ORF)突变,分析其对HIV传播和致病的影响。方法研究对象为居住在香港的1099名成年中国人,其中785人为HIV阴性健康人,另外314人为确诊HIV感染的患者。通过对非同义突变CCR5 ORF进行完整测序,确定并分析CCR5突变在人群的分布。结果在CCR5 ORF共检测到10个突变,其中7个为非同义突变;突变R223Q是发生频率最高的突变,在正常人是4.7%,在HIV患者是4.5%;发生频率第二的突变是299(FS),在正常人是0.89%,在HIV患者是1.59%;其余CCR5 ORF突变发生频率均小于1%;突变G106R位于CCR5第三跨膜区,该突变可能通过影响ECL2结构而影响其辅助受体功能。结论CCR5 ORF突变在中国人群较为常见,一些突变可能影响其作为HIV辅助受体的功能,但在流行病学范围内对HIV感染及致病的影响不明显。

Study of Naturally Occurring Mutations in Open Reading Frame of CCR5 in Hong Kong Chinese

Objective To determine the polymorphism of HIV co-receptor, CC chemokine receptor 5(CCR5) in Chinese and its effects on HIV infection. Methods Two groups of Chinese residing in Hong Kong were recruited: ① 785 HIV-healthy donors and ② 314 HIV+ patients. CCR5 mutations were identified from the study subjects by full sequencing of the open reading frame(ORF). Results Ten mutants of CCR5 ORF were identified, seven of which were non-synonymous. Two previously reported mutants, R223Q and 299(FS) were proved to be the most prevalent. These alleles did not show significant difference between HIV patients and healthy controls. However, the novel mutant G106R might affect the conformation in the second extra-cellular loop(ECL2) of CCR5 and change its co-receptor function. Conclusion Mutation in the CCR5 ORF is quite prevalent in ethnic Chinese. However, the identified mutants do not affect HIV infection from epidemiological level. Structural analysis had indicated that the novel mutant G106R in the third trans-membrane domain might affect its function as co-receptor for HIV.