MST-4基因启动子多态位点与AD的相关性研究

目的 探讨MST-4(丝/苏氨酸蛋白激酶-4)基因启动子区多态性、载脂蛋白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377例日本人AD患者,包括324例迟发型AD(LOAD)与53例早发型AD(EOAD)和379例非痴呆对照组中观察MST4基因启动子rs2748729(-3507A/G)及APOE基因的多态性分布,并分析与AD的相关性.结果 (1)MST4基因启动子rs2748729上G/G纯合子频率在AD中明显低于对照组(0.28比0.35,P值为0.038);同样趋势见于LOAD,EOAD与对照组,但P值均>0.05;(2)进一步在非APOE4携带者中比较发现rs2748729上G/G纯合子频率在AD中亦低于对照组(0.27比0.35),但P值为0.078;(3)进一步性别分层分析发现女性群体中rs2748729上G/G纯合子频率在AD与对照组中无显著性差异.结论 MST-4基因启动子rs2748729多态位点与AD存在微弱相关性,G/G纯合子具有一点的保护作用,但这种相关性不表现在女性人群中,需在大样本、多中心人群中进一步去阐明.

Association of MST4 gene promoter polymorphisms with Alzheimer's disease

Objective To explore the association of MST4（Serine/threonine--protein kinase） gene promoter and APOE polymorphisms with Alzheimer＇s disease. Methods Using the single nucleotide poly- morphism（SNP） and TaqMan-PCR method the polymorphisms of MST4 gene in promoter（rs2748729（- 3507A/G）） and APOE were analyzed in 377 AD（including 324 late--onset AD（LOAD） cases and 53 early-onset AD（EOAD） cases） and 379 non--demented controls in Japanese population. Results （1）The frequencies of GG genotype in AD rs2748729 （-3507A/G） were significant lower than those in controls （0.28： 0.35, P values were 0. 038）, the same results can been seen among LOAD, EOAD, but P 〉 0.05 （2）Further comparative analysis between AD and controls among Non--APOE4 individuals showed that negative association of AD with rs2748729 GG genotype（ P values were 0. 078）. （3） Comparative analysis between AD and controls among female individuals demonstrated that negative association of AD with rs2748729 GG genotype. Conclusions The polymorphisms in promoter of MST4 were weakly significantly associated with lower AD risk, but it was negative result among female individuals,The ongoing investigation of the association in a larger sample and different ethnicities is warranted.