胰岛素信号转导通路相关基因多态性与阿尔茨海默病的关系

Relationship between insulin signal transduction pathway-associated gene polymorphism and Alzheimer disease

目的探讨胰岛素信号转导通路相关基因胰岛素磷脂酰肌醇3激酶(PI3K)多态性与阿尔兹海默病(AD)之间的关系。方法选择AD患者231例(AD组)、健康对照者231名(健康对照组)为研究对象,提取研究对象外周静脉血全血样本的DNA,通过PCR法和单核苷酸多态性测序检测PI3K多态性,同时利用ELISA检测其血清PI3K的蛋白水平,比较2组PI3K基因型和等位基因分布情况以及PI3K蛋白水平的差异,并分析PI3K多态性rs3730087与PI3K蛋白表达水平的关系。结果 2组PI3K多态性参考ID PIK3R1 rs3730087的各基因型和等位基因以及PI3K蛋白水平比较差异均具统计学意义(P均<0.05)。2组内不同基因多态性的PI3K蛋白表达水平比较差异均有统计学意义,其中AD组TT和TC比较的P为0.004、TT和CC比较的P为0.016,健康对照组TT和TC比较的P为0.001、TT和CC比较的P为0.022。结论胰岛素信号转导通路相关基因PI3K多态性与AD有一定关系,PIK3R1 rs3730087(T>C)增加了AD的患病风险。

Objective To investigate the relationship between insulin signal transduction pathway-associated gene phosphatidylinositol 3 kinase （PI3K） polymorphism and Alzheimer disease （AD）.Methods In this study, 231 AD patients（AD group） and 231 healthy subjects （healthy control group） were recruited.Peripheral venous blood sampling was collected for DNA detection.The gene polymorphism of PI3K was detected by PCR and single nucleotide polymorphism sequencing.The serum level of PI3K protein was measured by enzyme linked immunosorbent assay （ELISA）.The PI3K genotype, allele distribution and PI3K protein level were statistically compared between two groups.The relationship between PI3K polymorphism rs3730087 and expression level of PI3K protein was analyzed.Results The genotype and allele of PI3K polymorphism reference IDPIK3R1 rs3730087 and the PI3K protein level significantly differed between the AD and healthy control groups （P〈0.05）.The expression levels of PI3K protein with varying gene polymorphisms significantly differed between TT and TC （P=0.004）, TT and CC in the AD group （P=0.016）, TT and TC（P=0.001）, TT and CC（P=0.022）in the healthy control group.Conclusions The insulin signal transduction pathway-associated gene PI3K polymorphism exerts certain effect upon AD.PIK3R1 rs3730087 （T〉C） increases the risk of AD.