新疆维吾尔族人自然长寿与HLA-DRB,ACE,ApoE基因多态性分析  

Association of polymorphisms of HLA-DRB gene, ACE gene, and ApoE gene with natural longevity in the Xinjiang Uighur people

作　　者：热米拉.巴力 吐尔洪.吐尔逊 陈凤辉[1] 程祖亨[1] 邱长春[3] 玛依拉.吾甫尔 

机构地区：[1]新疆医科大学第一附属医院综合心脏内科,830054 [2]新疆医科大学第一附属医院神经内科,830054 [3]中国医学科学院中国协和医科大学基础医学研究所医学分子生物学国家重点实验室

出　　处：《北京医学》2014年第7期525-529,共5页Beijing Medical Journal

基　　金：国家自然科学基金(31160215)

摘　　要：目的：探讨人类白细胞抗原（human leukocyte antigen, HLA）基因、血管紧张素转换酶（An-giotensin-Coverting Enzyme, ACE）基因及载脂蛋白E（Apolipoprotein E, ApoE）基因多态性与新疆维吾尔族自然长寿的关系。方法将研究对象根据年龄分为长寿组和老年组，同时选择同一地区无血缘关系已自然死亡（61-73岁）者为对照组。分别应用聚合酶链反应-序列特异引物法（PCR-SSP），单链构象多态性（SSCP）分析和直接测序技术对长寿组、老年组、对照组进行基因分型。结果长寿组HLA-DR1，DR6（14）基因频率较对照组升高（P〈0.05），与老年组比较差异无统计学意义；长寿组HLA-DR9基因频率较对照组降低（P〈0.05），较老年组显著降低（P〈0.01）；长寿组HLA-DR51基因频率较老年组降低（P〈0.05），与对照组比较差异无统计学意义。在ACE基因分析中，长寿组D/D基因型频率较对照组显著升高（P〈0.01），而较老年组升高（P〈0.05），另外，长寿组D等位基因频率也高于对照组（P〈0.05），与老年组比较差异无统计学意义；另外，3组间DI，Ⅱ基因型比较未见明显差异。 ApoE基因分析中，长寿组ε3/3基因型频率较老年组升高（P〈0.05），与对照组比较差异无统计学意义；长寿组ε4/3基因型频率较对照组明显降低（P〈0.001），较老年组也显著降低（P〈0.01）；其余基因型比较差异无统计学意义。结论 HLA-DRB基因的DR1,DR6（14）等位基因，ApoE的ε4/3基因型及ACE基因的DD基因型，D等位基因对长寿可能有保护作用，是长寿有利基因；HLA-DRB基因的DR9基因型可能不利于长寿，是长寿的危险因素。Objectives To explore the potential relationship among the polymorphisms of HLA-DRB gene, ACE gene, and ApoE gene linked to natural longevity in the Xinjiang Uighur nationality people. Methods The study population was divided into three groups： the longevity group, the older age group and the control group. Using PCR-SSP, SSCP （single strand conformation polymorphism） and direct sequencing technique respectively to genotype each group. Results The frequency of HLA-DR1, DR6（14） in the longevity group was higher than the control（P〈 0.05）, but no significant dif-ference could be found when compared with the older age group. The frequency of HLA-DR9 in the longevity group was lower than the control （P〈0.05）, which was significantly lower than the older age group （P〈0.01）. The frequency of HLA-DR51 in the longevity group was lower than the older age group （P〈 0.05）, but no significant difference could be found when compared with the controls. The frequency of ACE DD genotype in the longevity group was significantly higher than the control （P〈0.01）, the older age group （P〈0.05）, and the frequency of D allele in the longevity group was higher than the control（P〈0.05） but no significant difference was detected when compared with the older age group. There was no significant difference in the frequencies of other genotypes between three groups; The frequency of ApoE ε3/3 genotype in the longevity group was higher than the older age group （P〈 0.05）, but no significant difference when compared with the controls. The frequency of ApoEε3/4 genotype in the longevity group was significantly lower than the control and the older age group （P〈 0.001, P〈 0.01）. There was no significant difference between the three groups in the frequencies of other genotypes; Conclusion HLA-DR1, DR6 （14） genotype, ApoE ε3/4 genotype and ACE DD genotype, D allele might be the favorable genes of human longevity;and HLA-DR9 genotype might be deleterious gene of human longevity.

关 键 词：人类白细胞抗原 血管紧张素转换酶 载脂蛋白E 新疆维吾尔族 自然长寿 

分 类 号：R339.36[医药卫生—人体生理学]