烟酰胺腺嘌呤二核苷酸磷酸:醌氧化还原酶1基因多态性与认知功能减退和老年性痴呆的关系

目的分析烟酰胺腺嘌呤二核苷酸磷酸:醌氧化还原酶1(NQO1)基因多态性与认知功能减退和阿尔茨海默病(AD)发病的关系.方法经多聚酶链反应扩增后,用变性高效液相色谱和DNA自动测序等方法,分析来自流调人群的110例简易精神状态量表(MMSE)评分正常者,21例评分低于正常但非AD者,以及65例AD患者C609T多态性位点分布频率的差异.结果MMSE评分正常组与低于正常组NQ01基因C609T位点基因型分布差异有显著性(P＜0.05),携带T/T或C/T基因型者患认知功能减退的危险性增高(0R=2.8,95%CI 0.96～8.18,P=0.024).T等位基因频率在AD组(53%)显著高于对照组(38%)(0R=1.87,95%CI 1.20～2.90,P=0.005),T/T和C/T基因型在AD组(83%)和对照组(60%)之间差异亦有显著性(OR=3.27,95%CI 1.54～6.94,P=0.001).结论NQD1基因C609T多态位点可能是认知功能减退和散发性AD的一个共同危险因素.

NQ01 gene polymorphism C609T associated with an increased risk for cognitive dysfunction and sporadic Alzheimer's disease in Chinese

Objective To investigate the association between the C609T polymorphism of NADP(H): quinoneoxidoreductase 1(NQO1)gene and decreased cognitive function and sporadic Alzheimer's disease(AD)in a community cohort. Methods Polymerase chain reaction(PCR), denaturing high performance liquid chromatography(DHPLC)and sequencing were used to determine the genotype of NQO1 in 110 subjects without cognitive dysfunction, 21 with cognitive dysfunction, and 65 AD patients from a community cohort. Results Significantly different distributions of C/T and T/T genotypes were found between MMSE normal and abnormal subjects(OR=2.8, 95%CI 0.96-8.18,P = 0.024), and between AD patients and healthy controls(OR=3.27, 95%CI 1.54-6.94, P =0.001), respectively. The frequencies of T allele of NQO1 C609T were significantly higher in MMSE abnormal subjects and AD patients(P = 0.034 and 0.005)as compared to normal controls. Conclusion The C609T polymorphism of NQO1 gene may be a genetic risk factor for cognitive dysfunction and sporadic AD in Chinese population.