摘要
目的探讨载脂蛋白E基因多态性和中国汉族阿尔茨海默病（AD）患者发病年龄的相关性。方法研究对象来源于北京协和医院认知障碍门诊1999--2010年连续就诊的495例很可能AD患者，根据发病年龄分为早发性AD（EOAD，发病年龄〈65岁）和晚发性AD（LOAD，发病年龄≥65岁）。应用聚合酶链反应-限制性片段长度多态性分析法检测ApoE基因型。应用单因素方差分析不同基因型和AD发病年龄的相关性，应用一般线性模型分析AD患者发病年龄的影响因素。结果495例AD发病年龄为（69±10）岁，其中149例EOAD的发病年龄为（58±5）岁，而346例LOAD的发病年龄为（74±6）岁。不同的ApoE基因型与早发性AD患者发病年龄无统计学相关性[ε4-／-：（57±5）岁，n=90；ε4＋／-：（59±5）岁，n=50；ε4＋／＋：（59±5）岁，n=9；F=0．99，P=0．38]，而携带ApoEε4的基因型与晚发性AD患者的发病年龄存在统计学相关性[ε4-／-：（75±6）岁，n=189；ε4＋／-：（73±6）岁，n=138；ε4＋／＋：（71±5）岁，n=19；F=6．51，P=0．002]。晚发性AD患者中，5种基因型发病年龄总体比较差异有统计学意义，发病年龄从大到小依次是ε2／3〉ε3／3〉ε3／4〉ε2／4〉ε4／4。在LOAD患者中，无痴呆家族史者不同基因型发病年龄差异有统计学意义（F=5．18，P〈0．01），而有痴呆家族史者不同基因型发病年龄差异无统计学意义（F=1．73，P〉0．05）。结论携带ε4的ApoE基因型可能降低了中国汉族晚发性AD患者发病年龄，呈现ε4剂量依赖效应。而在具有痴呆家族史患者中未观察到这种效应。
Objective To investigate the correlation between the ApoE genotype and age at onset in a cohort of hospital- based AD patients of Han population in China. Methods All cases were consecutive probable AD patients from the Memory and Cognitive Impairment Clinic of Peking Union Medical Collge Hospital from 1999 to 2010. They were all Han ethnicity. They were divided into two groups according to age at onset（AAO） ： early onset AD （ EOAD, AAO 〈 65 years） and late onset AD （LOAD, AAO 〉165 years）. DNA was extracted and ApoE was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. The linkage between ApoE polymorphism and AAO of AD were analyzed by one-way ANOVA. Results AAO of all cases（n =495） was （69±10） years,of EOAD（n = 149） was （58 ±5）years and of LOAD （ n = 346） was （74± 6） years. ApoEε4 （ ＋ ） genotypes were not associated with AAO of EOAD [ε4-/- ：（57 ±5） years,n=90;ε4 ＋/- ：（59 ±5） years,n =50;ε4 ＋/＋ ：（59±5） years,n =9;F = 0. 99 ,P =0. 38] ,while they were significantly associated with AAO of LOAD[ ε4 -/- ： （ 75 ±6） years, n =189; ε4 ＋/- ：（73±6） years,n = 138;ε4 ＋/＋ ：（71±5） years,n=19;F=6.51,P=0. 0021. As for all ApoE genotypes, AAO of LOAD reduced gradually in a way as follows ： ε2/3 〉 ε3/3 〉 ε3/4 〉 ε2/4 〉 ε4/ 4. There was great correlation between AAO and ApoE polymorphism in LOAD without dementia family history,whereas no correlation in LOAD with dementia family history. Conclusion ApoE genotypes carrying at least oneε4 allele maybe significantly lower AAO of LOAD in a dose-dependent manner whereas no such correlation in LOAD with dementia family history.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2013年第3期182-186,共5页
National Medical Journal of China
