中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2013年
3期
182-186
,共5页
王景涛%李凌%袁晶%张振馨
王景濤%李凌%袁晶%張振馨
왕경도%리릉%원정%장진형
阿尔茨海默病%载脂蛋白E%基因多态性%发病年龄
阿爾茨海默病%載脂蛋白E%基因多態性%髮病年齡
아이자해묵병%재지단백E%기인다태성%발병년령
Alzheimer's disease%Apolipoprotein E%Gene polymorphism%Age at onset
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.
目的 探討載脂蛋白E基因多態性和中國漢族阿爾茨海默病(AD)患者髮病年齡的相關性.方法 研究對象來源于北京協和醫院認知障礙門診1999-2010年連續就診的495例很可能AD患者,根據髮病年齡分為早髮性AD(EOAD,髮病年齡＜65歲)和晚髮性AD(LOAD,髮病年齡≥65歲).應用聚閤酶鏈反應-限製性片段長度多態性分析法檢測ApoE基因型.應用單因素方差分析不同基因型和AD髮病年齡的相關性,應用一般線性模型分析AD患者髮病年齡的影響因素.結果 495例AD髮病年齡為(69±10)歲,其中149例EOAD的髮病年齡為(58±5)歲,而346例LOAD的髮病年齡為(74±6)歲.不同的ApoE基因型與早髮性AD患者髮病年齡無統計學相關性[ε4-/-:(57±5)歲,n =90;ε4+/-:(59 ±5)歲,n=50；ε4+/+:(59±5)歲,n=9;F=0.99,P=0.38],而攜帶ApoEε4的基因型與晚髮性AD患者的髮病年齡存在統計學相關性[ε4-/-:(75±6)歲,n=189;ε4+/-:(73±6)歲,n=138;ε4+/+:(71 ±5)歲,n=19;F=6.51,P=0.002].晚髮性AD患者中,5種基因型髮病年齡總體比較差異有統計學意義,髮病年齡從大到小依次是ε2/3＞ ε3/3＞ ε3/4＞ ε2/4 ＞ε4/4.在LOAD患者中,無癡呆傢族史者不同基因型髮病年齡差異有統計學意義(F=5.18,P＜0.01),而有癡呆傢族史者不同基因型髮病年齡差異無統計學意義(F=1.73,P＞0.05).結論 攜帶ε4的ApoE基因型可能降低瞭中國漢族晚髮性AD患者髮病年齡,呈現ε4劑量依賴效應.而在具有癡呆傢族史患者中未觀察到這種效應.
목적 탐토재지단백E기인다태성화중국한족아이자해묵병(AD)환자발병년령적상관성.방법 연구대상래원우북경협화의원인지장애문진1999-2010년련속취진적495례흔가능AD환자,근거발병년령분위조발성AD(EOAD,발병년령＜65세)화만발성AD(LOAD,발병년령≥65세).응용취합매련반응-한제성편단장도다태성분석법검측ApoE기인형.응용단인소방차분석불동기인형화AD발병년령적상관성,응용일반선성모형분석AD환자발병년령적영향인소.결과 495례AD발병년령위(69±10)세,기중149례EOAD적발병년령위(58±5)세,이346례LOAD적발병년령위(74±6)세.불동적ApoE기인형여조발성AD환자발병년령무통계학상관성[ε4-/-:(57±5)세,n =90;ε4+/-:(59 ±5)세,n=50；ε4+/+:(59±5)세,n=9;F=0.99,P=0.38],이휴대ApoEε4적기인형여만발성AD환자적발병년령존재통계학상관성[ε4-/-:(75±6)세,n=189;ε4+/-:(73±6)세,n=138;ε4+/+:(71 ±5)세,n=19;F=6.51,P=0.002].만발성AD환자중,5충기인형발병년령총체비교차이유통계학의의,발병년령종대도소의차시ε2/3＞ ε3/3＞ ε3/4＞ ε2/4 ＞ε4/4.재LOAD환자중,무치태가족사자불동기인형발병년령차이유통계학의의(F=5.18,P＜0.01),이유치태가족사자불동기인형발병년령차이무통계학의의(F=1.73,P＞0.05).결론 휴대ε4적ApoE기인형가능강저료중국한족만발성AD환자발병년령,정현ε4제량의뢰효응.이재구유치태가족사환자중미관찰도저충효응.
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＞65 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 =0.002].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.
