胆固醇24S-羟化酶基因多态性与散发性阿尔茨海默病的相关性研究  

Study on relation between cholesterol 24S-hydroxylase polymorphism and sporadic Alzheimer's disease

作　　者：赵发国[1] 石进[1] 王荫华[2] 冯秀丽[3] 杨静芳[4] 汤哲[4] 刘宏军[4] 马秋兰[4] 陈彪[4] 

机构地区：[1]空军总医院神经内科,北京100142 [2]北京大学第一医院神经内科 [3]国家人类基因组北方研究中心 [4]首都医科大学宣武医院神经生物学部神经内科

出　　处：《中华老年心脑血管病杂志》2010年第10期921-924,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家科技攻关计划(2002BA711A10);国家科技攻关计划(2002BA711A07-04);国家高技术研究发展计划(2002AA2Z2011);北京市科技计划(H020220020610)

摘　　要：目的探讨胆固醇24S-羟化酶（CYP46）基因多态性是否为散发性阿尔茨海默病（SAD）的遗传易感基因。方法选择SAD患者108例作为SAD组，同期选择年龄、性别相匹配的健康老年人118例作为对照组，用变性高效液相色谱法对CYP46基因的核苷酸序列进行扫描，比较2组变异位点的基因型和等位基因频率分布。结果在外显子-内含子交界区检出10个不同的变异位点，5个多态性位点（IVS2～150A〉G，IVS3＋43C〉T，IVS3—130C〉T，IVS5＋51G〉C，IVS7—65T〉C）是较好的遗传标记。SAD组和对照组在IVS2—150A〉G基因型AG＋GG的分布频率差异无统计学意义（χ^2=1．369，P=0．242）；SAD组和对照组等位基因G的分布频率差异无统计学意义（χ^2=0．003，P=0．956）。SAD组和对照组携带载脂蛋白E（apoE）ε4与非携带apoEε4者上述基因分布差异均无统计学意义（P〉0．05）。IVS2-150A〉G与SAD无相关性。结论CYP46是一个较为保守的基因，其内含子2上的多态性位点IVS2-150A〉G与SAD的发病无关。Objective To investigate the association of polymorphism of CYP46 gene of cholesterol 24S-hydoxylase with sporadic Alzheimer＇s disease（SAD）. Methods 108 SAD patients were selected as SAD group and 118 age and gender-matched healthy elderly served as control group. The sequence variants were analyzed by denaturing high performance liquid chromatography. The differences in the distribution of genotype or allele between the 2 groups were compared. Results Ten different suquence variants of CYP46 were identified,of which five SNPs（IVS2-150A〉G, IVS3＋43C〉T, IVS3 - 130C〉 T, IVS5 ＋ 51G〉C, IVS7 - 65T〉C） were good genetic markers. No statistical difference was observed in genotype （P = 0. 242） or allele frequencies （P = 0. 956） for intron 2 polymorphism IVS2-150A〉G between the 2 groups. When data were stratified by apoEε4 carrier status,no statistical difference was observed either. Conclusion The data of present study suggest that CYP46 is a conservative gene. The intron 2 polymorphism IVS2-150A〉G does not affect the risk of SAD in northern ethnic Han Chinese population.

关 键 词：阿尔茨海默病 甾类羟化酶类 多态性 单核苷酸 色谱法 高压液相 胆固醇24S-羟化酶 

分 类 号：R749.19[医药卫生—神经病学与精神病学]