【摘要】 目的探讨淋巴细胞特异性酪氨酸蛋白激酶(LCK)基因多态性、载脂蛋白E(apoE)基因多态性和阿尔茨海默病(AD)的相关性。方法用Taq Man-PCR法检测单核苷酸多态性(SNP),对380例日本人AD患者[包括327例迟发型AD(LOAD)与53例早发型AD(EOAD)]和380例非痴呆对照组中,观察LCK基因及apoE基因的多态性分布,并分析其与AD的相关性。结果(1)LCK基因+6424A/G多态位点的G/G基因型患AD风险为非G/G型的1.41倍(95%CI=1.06~1.87),患LOAD风险为1.37倍(95%CI=1.02~1.85);(2)apoEε4基因携带者患AD风险为非apoEε4基因携带者的5.11倍(95%CI=3.63~7.19);(3)排除apoE基因型对AD风险的影响后,G/G基因型患AD风险为非G/G型的1.66倍(95%CI=1.16~2.38),患LOAD风险为1.64倍(95%CI=1.12~2.40),同时风险等位基因G与AD(P<0.05)和LOAD(P<0.05)具有相关性。结论LCK基因+6424A/G多态位点与AD风险的增加呈正性相关性,apoEε4增加了AD的发病风险,LCK是独立于APOE基因的又一新的风险基因。更多还原

【Abstract】 Objective To explore the association of polymorphisms of lymphocyte-specific protein tyrosine kinase (LCK) and APOE in Alzheimer disease. Methods Using the single nucleotide polymorphism (SNP) and TaqMan-PCR method the polymorphism of LCK in intron 1 (+6424 A/G) and APOE were analyzed in 380 AD (including 327 late-onset AD (LOAD) cases and 53 early-onset AD (EOAD) cases) and 380 non-demented controls in Japanese population. Results (1) The odds ratio (OR) for total AD associated with the G/G genotype was 1.41 (95% CI=1.06~1.87) and that for LOAD was 1.37 (95%CI=1.02~1.85). (2) The odds ratio (OR) for total AD associated with APOE-ε 4 was 5.11 (95% CI=3.63~7.19). (3)After excluding the effect of APOE-ε4, the G/G genotype also showed significant association with AD(OR=1.66,95% CI=1.16~2.38) and LOAD (OR= 1.64,95% CI=1.12~2.40);The risk allele-G is significantly associated with AD (P<0.05) and LOAD (P<0.05). Conclusions The polymorphism in intron 1 (+6424 A/G) of LCK was significantly associated with AD risk,APOE-ε4 conferred an increased risk for AD,LCK is a novel risk gene for AD regardless of the APOE genotype.更多还原