朊蛋白基因多态性与老年性痴呆的相关性研究

Correlation of Prion Protein Gene Polymorphism with Alzheimer Disease

目的探讨朊蛋白基因(PRNP)129密码子多态性与老年性痴呆(AD)发病的相关性。方法采用病例-对照研究方法,以PCR-RFLP方法检测驻京部队干休所60例晚发AD(LOAD)患者与92例健康老年对照的PRNP129密码子基因、ApoEε4等位基因多态性。结果驻京部队干休所汉族老年人群中PRNP129密码子甲硫氨酸纯合(MM)基因型频率为94.08%,甲硫氨酸缬氨酸杂合(MV)基因型频率为5.92%,未发现缬氨酸纯合(VV)型。ApoEε4等位基因分层前后,MM基因型发生LOAD的风险性差异无统计学意义。PRNP129密码子MM型不是LOAD的独立危险因素(OR=3.27,95%CI=0.402～26.605)。结论东亚人群与欧洲人群PRNP129密码子多态性分布不同。PRNP129密码子MM基因型携带者发生LOAD的风险无显著增高,提示MM基因型不参与LOAD发病。

Objective To investigate the correlation between codon 129 polymorphism of prion protein gene （PRNP） and onset of Alzheimer Disease. Methods The polymorphism of PRNP codon 129 was investigated by PCR-RFLP in a total of 152 senile Han subjects of the military health-care population in Beijing, which was composed of 92 cognitively healthy controls, 60 individuals with a clinical diagnosis of late onset AD. ApoE gene polymorphism was also detected for stratification. Results The genotype frequencies of PRNP codon 129 were 94.08% Methione Homozygote（MM）, 5.92% Methione-Valine Heterozygote（MV） and 0% Valine Homozygote （VV）, with distribution of 95% MM and 5% MV in LOAD group. The risk of MM carrier for LOAD had no statistical significance before or after stratification by ApoEε4. Logistic regression analysis using age, gender and ApoEε4 allele as covariates showed OR value of 3.27（95 %CI=0. 402-26. 605, P=0. 2627 ） of MM genotype for LOAD. Conclusions PRNP codon 129 polymorphism of East Asia population was significantly different from that of Europe. The risk for LOAD of individuals carrying PRNP codon 129 MM genotype was not increased significantly. PRNP codon 129 MM genotype was not an isolated risk factor for onset of LOAD.