胆固醇24S-羟化酶基因多态性与阿尔茨海默病的相关性分析

An intronic cholesterol 24S-hydroxylase polymorphism associated with Alzheimer disease

目的探讨胆固醇24S－羟化酶（cholesterol 24-hydroxylase，CYP46）基因第二内含子单核苷酸多态性（single nucleotide polymorphism，SNP）与阿尔茨海默病（AD）的相互关系。方法采用等位基因特异性聚合酶链反应（allele—specific PCR，A—SPCR）技术检测508例AD患者和549名健康老年人CYP46基因第二内含子基因SNP的分布，并通过比值比（OR）做疾病关联分析。结果AD组与对照组CYP46基因SNP分布差异有统计学意义（12，9％，8．1％；X^2=6．59，P=0．037），AD组携带T等位基因（C／T＋T／T）频率明显高于健康对照组（91．9％，87．0％；X^2=6，58，P=0．01）。Logistic回归分析表明，C／T和T／T基因型均是AD的危险因素，调整年龄和性别的影响后，其OR值分别为：1．70（95％CI=1．10—2．63，C／T），1．69（95％ CI=1．10—2．59，T／T）。结论CYP46基因的SNP与AD存在相关性，携带T等位基因可能是AD的危险因素。

Objective To evaluate the association of an intronic single nucleotide polymorphism （SNP） in cholesterol 24S-hydroxylase 0（CYP46） gene with Alzheimer＇s disease （AD） in Chinese Han population. Methods An intronic SNP of CYP46 gene was detected by Allele-Specific PCR （A-S PCR） technique in 508 patients with AD and 549 controls. Results The distribution of CYP46 genotypes was significantly different in AD patients as compared to the controls （ 12.9% vs 8.1% ; X^2 = 6.59, P = 0. 037）. The presence of at least one of CYP46 T allele （C/T or T/T） was higher in AD patients than the controls（91.9% vs 87. 1% ; X^2 =6.58, P =0. 01 ）. One-Way ANOVA showed that CYP46 genotype had no effects on the age of onset of AD. Logistic regression analysis demonstrated the age and sex-adjusted OR for the risk of AD in CYP46 C/T and in CYP46 T/T genotype were 1.70 （95% CI = 1.10-2. 63 ） and 1.69 （95% CI = 1.10-2.59） respectively. Condusion This intronic SNP in CYP46 gene is associated with AD in Chinese Han population, and the T allele might be a risk factor for AD.