淀粉样前体蛋白基因启动子区-2335C/T和+37C/G基因多态性与Alzheimer病的关系

Association of the polymorphisms of the -2335C/T and +37C/G genes in amyloid precursor-protein promoter region with susceptibility to Alzheimer's disease

目的:探讨淀粉样前体蛋白(APP)基因启动子区-2335C/T(rs364091)和+37C/G(rs459543)位点基因多态性与Alzheimer病(AD)的相关性。方法:采用酶联免疫吸附试验(ELISA)检测85例AD患者(AD组)及85名健康老年志愿者(对照组)的APP基因启动子区-2335C/T和+37C/G位点基因型,并检测其血清APP蛋白的表达。结果:AD组-2335C/T位点TT基因型和T等位基因频率、以及+37C/G位点GG基因型及G等位基因频率显著高于对照组(P<0.05或P<0.01);多因素Logistic回归分析结果显示,-2335C/T位点TT基因型及T等位基因、以及+37C/G位点GG基因型及G等位基因携带者AD患病风险显著升高(校正后OR=1.778,95%CI:1.151～2.267,P=0.011;校正后OR=1.451,95%CI:1.141～1.765,P=0.002;校正后OR=1.596,95%CI=1.008～2.103,P=0.046;校正后OR=1.338,95%CI:1.052～1.644,P=0.018)。AD组血清APP水平[(7.58±1.45)ng/L]显著高于对照组[(5.95±1.31)ng/L](P<0.01);APP基因-2335C/T位点以及+37C/G位点纯合型、杂合型、野生型血清APP表达水平均逐渐升高,两两比较差异均有统计学意义(P均<0.01)。结论:APP基因启动子区-2335C/T位点和+37C/G位点基因多态性与中国人AD易感性有关,其机制可能是调控APP表达。

Objective: To study the association between gene polymorphisms of the -2335C/T(rs364091) and+37C/G(rs459543) loci in the promoter region of amyloid precursor-protein(APP) gene and susceptibility to Alzheimer disease. Method: Eighty-five patients with Alzheimer's disease(AD) who were admitted to our hospital from May 2014 to May 2017 were randomly selected as the study group(AD group).In the same period,85 elderly people undergoing physical examination in our hospital were recruited as a healthy control group.Enzyme-linked immunosorbent assay(ELISA) was used to detect the genotypes of -2335C/T and +37C/G in APP promoter regions of all subjects.The expression of APP protein in the subjects' serum was measured. Results: Multivariate Logistic regression analysis showed that the risk of AD was significantly higher in the -2335C/T locus T allele and the+37C/G locus G allele carriers(adjusted OR = 1.778,95%CI: 1.151- 2.267, P =0.011;adjusted OR =1.451,95% CI:1.141-1.765,P =0.002;adjusted OR =1.596,95%CI:1.008-2.103, P =0.046;adjusted OR =1.338,95% CI=1.052-1.644,P = 0.018 ).The serum APP protein level in the AD group was significantly higher than that in the control group [(5.95±1.31) ng/L vs.(7.58±1.45) ng/L],and the difference was statistically significant( P <0.01).The levels of APP protein in the homozygous,heterozygous,and wild-type individuals with the APP gene -2335 C/T and +37C/G mutations were gradually increased,and the difference between the each two genotype was statistically significant( P < 0.01). Conclusion: The gene polymorphisms at the -2335C/T and +37C/G locus in the APP gene promoter region are associated with AD susceptibility.The mechanism may be the regulation of APP protein expression.