胰岛素样生长因子1、载脂蛋白酶E基因多态性与阿尔茨海默病关系的研究

Association of the polymorphisms of IGF-1 gene,apolipoprotein E gene with Alzheimer's disease

目的探讨河南省汉族人群胰岛素样生长因子1(insulin like growth factor 1,IGF-1)基因rs972936位点多态性、载脂蛋白酶E(Apo E)基因多态性与阿尔茨海默病(Alzheimer’s disease,AD)之间的相关性。方法选取58例AD患者和126例年龄、性别相匹配的健康对照(ND)者为研究对象,柱层析法提取外周血基因组DNA,采用PCR和基因测序技术检测IGF-1基因rs972936位点及Apo E基因型多态分布,并进行对比分析。结果与ND组比较,AD组IGF-1基因rs972936位点3种基因型分布总体差异有统计学意义(χ~2=6.108,P=0.047),其中AD组中GG基因型的频率高于对照组(70.7%>51.6%,χ~2=5.935,P=0.015),G等位基因频率明显高于健康对照组(χ~2=6.502,P=0.011);AD组Apo Eε4等位基因频率可能增加AD的患病风险(OR=2.872,95%CI 1.542~5.351)(P=0.001);Apo Eε4等位基因不影响IGF-1基因rs972936位点的基因型或等位基因的分布频率(P>0.05)。结论 IGF-1基因rs972936位点多态性与河南汉族人群AD的发病可能有相关性,其中GG基因型、G等位基因可能是AD发病的独立于Apo Eε4等位基因的危险因素。Apo Eε4等位基因是散发性AD的主要危险因素。

Objective To explore the roles of the polymorphisms of insulin-like growth factor-1（ IGF-1） gene,the apolipoprotein E（ Apo E） gene in the development of Alzheimer＇s disease（ AD） in Han people of Henan province. Methods58 AD subjects and 126 sex-and age-matched healthy controls were enrolled in the study. Genomic DNAs were extracted from peripheral blood leucocytes by phenol-chloroform methods. The gene polymorphism distribution of the IGF-1（ rs972936） and Apo E（ ε2,ε3,ε4） were detected by polymerase chain reaction（ PCR） and gene sequencing. Results The distribution of IGF-1 rs972936 three genotypes（ GG,GA,AA） and two alleles（ G,A） was significantly different in AD patients as compared to the normal controls（ χ^2= 6. 108,P = 0. 047）,and the presence of the genotype GG and the allele G was higher in AD than normal controls（ 70. 7% 51. 6%,χ^2= 5. 935,P = 0. 015; χ^2= 6. 502,P = 0. 011）. The frequency of allele ε4 in patients with AD increased significantly compared with that of normal controls（ χ^2= 11. 722,P = 0. 001）.Allele ε4 of the Apo E increased the risk of Alzheimer＇s disease（ OR = 2. 872,95% CI 1. 542 - 5. 351,P = 0. 001）,while the allele ε3 of Apo E gene might be a protective factor（ OR = 0. 536,95% CI 0. 325 - 0. 886）. The presence of the ApoE ε4 allele did not influence IGF-1 rs972936 genotypes or allele distribution（ P〉 0. 05）. Conclusion The IGF-1 rs972936 may be association with AD and the genotype GG may be a risk factor of sporadic AD. The presence of the Apo E ε4 allele did not influence IGF-1 genotypes or alleles distribution. The allele ε4 of the Apo E is a major risk factor of sporadic AD while the allele ε3 of ApoE gene might be a protective factor.