肝脂酶-250G/A基因多态性与阿尔茨海默病相关性研究

摘要

目的:探讨常见肝脂酶启动子基因-250G/A多态性对阿尔茨海默病(AD)患者发病风险及认知功能的影响. 方法:采用病例对照研究,随机抽取湖南长沙地区汉族人群104例散发性AD患者(AD组)以及104名认知功能正常者(对照组)为研究对象,应用聚合酶链反应-限制性片段长度多态性方法测定肝脂酶-250G/A基因多态性,采用成人韦氏记忆量表(WMS)及威斯康辛卡片分类测验(WCST)进行认知功能测评. 结果:两组间GG、GA及AA 3种基因型分布差异有统计学意义(x2=7.925,P=0.019),其中AD组GG型频率显著高于对照组(27.9％和13.5％；x2 =5.233,P=0.022)；GA+AA型频率显著低于对照组(72.1％和86.5％；x2=6.595,P=0.016)；两组间等位基因频率比较差异无统计学意义(x2 =0.731,P＞0.05).肝脂酶A等位基因携带者(GA+ AA型)WMS的短时记忆能力得分显著增高(P＜0.05),而长时记忆和瞬时记忆能力得分差异无统计学意义(P＞0.05).多因素Logistic回归显示,A等位基因是AD的独立保护因素之一. 结论:肝脂酶-250G/A遗传变异与AD相关,A等位基因对AD发病及短时记忆功能可能有独立保护作用.%Objective: This study aimed to assess the effect of single-nucleotide polymorphism (SNP) in the hepatic lipase (HL) promoter - 250G/A on the risk of Alzheimers disease(AD) and cognitive function. Method:Using case-control study,a total of 104 sporadic AD patients and 104 individuals without cognitive impairment from a population of Chinese Han nationality in Changsha area was studied. The polymorphism of LIPC -250G/A was determined by the restriction fragment length polymorphism (RFLP) amplified by polymerase chain reaction ( PCR) . The evaluation of cognitive function was tested by Wechsler memory scale ( WMS) and Wisconsin card sorting test(WCST). Results: There were significant differences in the frequencies of three genotypes (GG,GA and AA) between AD patients and controls(x2 = 7. 925 ,P =0. 019) . The frequency of GG genotype in AD group was obviously higher than that of controls(27. 9% and 13. 5% ;x2=5. 233 ,P =0. 022). The frequency of GA + AA genotype in AD patients is significantly lower than that of controls (72.1% and 86. 5%; x2=6. 595 ,P = 0. 016). There was no significant difference in the frequency comparison of G allele and A al-lele(x =0. 731 ,P > 0. 05 ). Compared with GG genotype, the scores of short-term memory of GA + AA genotypes were higher( P < 0. 05 ) , but there was no significant difference in the score of long-term memory and transient memory(P >0. 05). Multi-factor logistic regression analysis showed that A allele was one of independent protective factors for AD. Conclusion: The genetic variation in hepatic lipase -250G/A was associated with AD, and A allele may provide a protective effect on the incidence of AD and short-term memory level.