ApoE基因多态性与长寿及长寿相关表型的关联研究及Meta分析

目的 该研究在多群体中筛查验证ApoE基因多态性与长寿的关联,并调查ApoE基因变异与长寿相关表型的关联.方法 该研究采用群体1筛查,群体2、3验证的策略,共收集814个长寿老人(年龄≥90岁)和1136个无长寿家族史、当地一般人群的对照组(年龄30～65岁).通过PCR-RFLP和测序方法对ApoE基因进行基因分型.结果 在3个群体中长寿老人的ApoE ε3/ε3频率明显高于对照人群,与长寿存在正关联,这个结果与以往其他群体的研究结果并不相同;而长寿老人中ApoE ε3/ε4 频率明显低于对照群体,与长寿存在负关联.同时,在长寿老人中,ApoE ε3/ε3携带者比未携带ApoEε3/ε3者的高密度脂蛋白水平高(F=6.970,P=0.005),ApoE ε4携带者(ε3/ε4和ε4/ε4基因型总和)比非ApoEε4携带者的总胆固醇和低密度脂蛋白水平高(F=4.810,P=0.003和F=4.21 8,P=0.012).另外,该文对世界不同群体进行Meta分析,结果显示ApoE ε4携带者与长寿负关联(合并OR=0.42,95%CI:0.36～0.49),是长寿的风险因素.ε3/ε3基因型与长寿正关联(合并 OR=1.47,95%CI:1.25～1.74),是长寿的保护因素.结论 多个群体验证ApoE ε3/ε3可能是长寿的保护因素,这与以往报道ApoE ε2/ε2是长寿保护因素的结果不同;而ApoEε4是长寿的风险因素.

Abstract：

Objective The present study is to identify and replicate the association of ApoE longevity in multi-populations, and observe the association of ApoE with longevity-related phenotype. Methods By multi-population design:identifying ApoE gene associated with longevity in population 1, and replicating ApoE gene associated with longevity in population 2 and 3. A total of 814 "longevity cases" were classified as participants who had survived to age 90 years or more, with a total of 1136" younger controls" less than 65 years of age. ApoE gene was genotyped by PCR-RFLP and sequencing. Results Results showed the homozygous ε3/ε3 genotype in long-lived population was significantly higher frequent than those in controls,positively associated with longevity, whereas the heterozygous ε3/ε4 genotype were significantly lower frequent than those in controls, negatively associated with longevity in 3 different populations. ApoE ε3/ε3 was associated with higher HDL-C levels(F=6.970,P=0.005),and ApoE ε4-carrier(the ε3/ε4 and ε4/ε4 genotypes) was associated with significantly higher TC and LDL-C levels(F=4.810,P =0.003 and F=4.218,P=0.012)in long-lived individuals.In addition, the meta-analysis in 14 populations in world suggested ε4-carriers were negatively associated with longevity(pool ORs=0. 42,95% CI:0. 36～0.49);whereas the ApoE ε3/ε3 genotype was positively associated (pool ORs=1.47,95% CI:1.25~1.74) with longevity. Conclusions It was confirmed ApoE gene was associated with longevity in multi-population. ApoE ε3 gene could conferred protective effect for healthy longevity which was inconsistent the previous results published , whereas ApoE ε4 gene increased the risk effect for successful aging and longevity.

The association of ApoE with longevity and longevity-related phenotype in multi-populations and Meta-analysis

Objective The present study is to identify and replicate the association of ApoE longevity in multi-populations, and observe the association of ApoE with longevity-related phenotype. Methods By multi-population design:identifying ApoE gene associated with longevity in population 1, and replicating ApoE gene associated with longevity in population 2 and 3. A total of 814 "longevity cases" were classified as participants who had survived to age 90 years or more, with a total of 1136" younger controls" less than 65 years of age. ApoE gene was genotyped by PCR-RFLP and sequencing. Results Results showed the homozygous ε3/ε3 genotype in long-lived population was significantly higher frequent than those in controls,positively associated with longevity, whereas the heterozygous ε3/ε4 genotype were significantly lower frequent than those in controls, negatively associated with longevity in 3 different populations. ApoE ε3/ε3 was associated with higher HDL-C levels(F=6.970,P=0.005),and ApoE ε4-carrier(the ε3/ε4 and ε4/ε4 genotypes) was associated with significantly higher TC and LDL-C levels(F=4.810,P =0.003 and F=4.218,P=0.012)in long-lived individuals.In addition, the meta-analysis in 14 populations in world suggested ε4-carriers were negatively associated with longevity(pool ORs=0. 42,95% CI:0. 36～0.49);whereas the ApoE ε3/ε3 genotype was positively associated (pool ORs=1.47,95% CI:1.25~1.74) with longevity. Conclusions It was confirmed ApoE gene was associated with longevity in multi-population. ApoE ε3 gene could conferred protective effect for healthy longevity which was inconsistent the previous results published , whereas ApoE ε4 gene increased the risk effect for successful aging and longevity.