TM4SF5基因与阿尔茨海默病的相关性研究

Association of TM4SF5 gene polymorphisms with Aizheimer＇s disease

目的探讨跨膜蛋白4超级家族5（transmembrane 4 superfamily member 5,TM4SF5）基因多态性、栽脂蛋白E（ApoE）基因多态性和阿尔茨海默病（AD）的相关性。方法通过使用TaqMan—PCR法检测单核苷酸多态性（SNP）方法，在376例日本人AD患者，包括323例迟发型AD（I。OAD）、53例早发型AD（EOAD）和377例非痴呆对照组中观察TM4SF5基因rs4790230（-791T／C）、rs746988（＋1528T／c）、rs2302328（＋11228c／A）及APOE基因的多态性分布，并分析与AD的相关性。结果（1）TM4SF5基因rs4790230（-791T／C）c／c纯合子频率在EOAD中明显高于对照组（0．70比0．52，P值为0．017）；rs2302328（＋11228C／A）携带A等位基因者频率在总AD中略高于对照组（0．88比0．84，P值为0．05）；（2）进一步在非APOE4携带者中分析显示rs4790230（-791T／C）c／c纯合子频率在EOAD中仍明显高于对照组（0．85比0．53，P〈0．001）；（3）单倍型分析显示病例组C—C—A型与C—T—A型频率分别高于时照组（0．29比0．21；0．35比0．16；P〈0．001）；病例组C—T—C型频率低于对照组（0．12比0．28；P〈0．001）。结论TM4SF5基因rs4790230（-791T／C）多态位点独立于APOE与EOAD存在相关性，三位点单倍型C—C—A型与C—T—A型增加了AD的发病风险。

Objective To explore the association of TM4SF5 （proteasome subunit-beta type-7） gene and APOE polymorphisms with Alzheimer＇s disease. Methods Polymorphisms of TM4SF5 gene （rs4790230（ -791T/C）. rs746988 （ ＋ 1528T/C）. rs2302328 （ ＋ 11228C/A） and APOE were analyzed in 376 AD （including 323 late-onset AD （LOAD） cases and 53 early-onset AD （EOAD） cases） and 377 non-demented controls in Japanese population using single nucleotide polymorphism （SNP） and Taq- Man-PCR method. Results The frequency of CC genotype was significantly higher in EOAD rs4790230 （-791T/C） than that in controls （0. 70：0.52, P values were 0. 017）. The frequency of A allele-carriers in AD rs2302328（-b 11228C/A） were higher than that in controls （0.88：0.84, P values were 0.05）. （2） Further analysis between AD and controls among Non-APOE4 individuals found that positive association of AD with rs4790230 （-791T/C）CC genotype （0. 85, 0. 53, P values were 0. 005）. Conclusions The polymorphisms of TM4SF5 （rs4790230 （-791T/C）） were significantly associated with EOAD which was independent of APOE gene, while haplotypes （C-C-A, C-T-A） increased the risk of AD.