ATP结合盒转运子1R219K基因多态性与阿尔茨海默病相关性研究

目的探讨胆固醇相关基因ABCA1外显子R219K遗传变异对阿尔茨海默病（AD）发病风险及认知功能的影响。方法采用病例对照研究方法测定湖南长沙地区汉族人群104例散发性AD患者以及104名60岁以上认知功能正常者的ABCA1R219K基因多态性。采用SPSS13．0软件进行统计分析。结果两组间RR、RK及KK3种基因型分布差异有统计学意义（Χ^2=8．777，P=0．012），AD组KK型频率显著低于对照组（Χ^2=5．261，P=0．022）。AD组（RK＋KK）型频率较对照组显著降低（54．8％＆70．2％，P=0．022）。KK型及K等位基因携带者血浆HDL-C、apoA-I水平增高，差异有统计学意义（P〈0．05）。在总体研究人群中，KK型及RK＋KK型携带者的MMSE评分以及WMS评分显著增高（P〈0．05）；进一步按照长时记忆、短时记忆和瞬时记忆3种记忆类型分析，与RR型相比，RK、KK型及RK＋KK型携带者的短时记忆及瞬时记忆得分显著增高（P〈0．05），而长时记忆得分的比较差异无统计学意义（P〉0．05）。Logistic回归结果表明K等位基因携带是AD发病的独立保护因素。结论ABCA1R219K变异与AD的发病有关，K等位基因携带对血脂及认知功能可能产生有益作用，并对AD的发生可能有一定保护作用。

Research on association between polymorphism of ATP-binding cassette transporter A1 and Alzheimer's disease

Objective To assess the effect of single-nucleotide polymorphisms （SNPs） in the cholesterol-related genes ABCA1 exon R219K variation on the risk of AD and cognitive function. Meth- ods Using case-control study, a total of sporadic 104 AD patients and 104 individuals above 60 years without cognitive impairment from a population of Chinese Han nationality in Changsha area were studied to determine the polymorphisms of ABCA1 R219K. Adopt SPSS 13. 0 for statistical analysis. Results There were significant differences in the frequencies of three genotypes （RR,RK and KK） between the AD patients and controls （Χ^2= 8. 777,P = 0. 012）. The frequency of KK genotype in AD group is obviously lower than that of controls （Χ^2= 5. 261 ,P =0. 022）. The frequency of KK＋RK genotype in AD patients was 54.8%, was significantly lower than that of controls （70.2%, P =0. 022）. There was significantly higher levels of HDL-C, apoA-I and cognitive scores in the carriers of KK genotype and K allele （P 〈 0.05）. There was significantly higher levels of MMSE and WMS scores in the carriers of KK genotype and K allele （P〈0.05）. Further in accordance with memory types including long-term memory, short-term memory, transient memory, compared with RR genotype, the scores of short-term memory, transient memory of RK, KK and RK＋KK genotypes were higher （P〈 0.05）, but there was no significant difference in the score of long-term memory （P 〉0.05）. Multifactor logistic regression analysis showed that carrying K allele was a single protective factor for AD. Conclusions The polymorphism of ABCA1R219K is associated with AD. Carrying K allele may play a positive role in serum lipids and cognition, and produce a protective effect on risk of AD.