阿尔茨海默病患者血脂水平与性别和年龄及载脂蛋白E基因多态性的相关研究

Correlation of serum lipids levels of Alzheimer′s disease patients with sex,age and apolipoprotein E gene polymorphism

目的探讨阿尔茨海默病(AD)患者血脂水平与性别、年龄及载脂蛋白E(Apo E)基因多态性的关系。方法采用回顾性研究方法,选择2015年1月至2021年8月在首都医科大学附属北京天坛医院就诊的407例AD患者(男性142例,女性265例,年龄52~91岁)作为研究对象,选择894名健康体检者(男性339名,女性555名,年龄52~94岁)为对照组,按照年龄间隔10岁将AD患者分为4个年龄段组,其中50~59岁85例,60~69岁163例,70~79岁119例,≥80岁40例。采用生化分析仪检测两组血脂水平,包括三酰甘油(TG)、胆固醇(CHO)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1(Apo A1)及载脂蛋白B(Apo B),采用实时荧光定量PCR方法检测Apo E基因多态性,采用Mann-Whitney U检验或Kruskal-Wallis H检验比较各组间血脂水平。结果AD患者的血清CHO为3.30(1.41,4.82)mmol/L,LDL-C为1.76(1.39,2.78)mmol/L,对照组CHO为4.84(4.24,5.56)mmol/L,LDL-C为2.91(2.36,3.57)mmol/L,AD患者CHO、LDL-C均低于对照组(Z=-15.172,Z=-14.583,P<0.001,P<0.001);AD患者的血清HDL-C为1.84(1.30,3.88)mmol/L,Apo B为1.17(0.85,1.57)g/L,对照组HDL-C为1.39(1.18,1.64)mmol/L,Apo B为0.93(0.81,1.09)g/L,AD患者HDL-C、Apo B均高于对照组(Z=-12.249,Z=-9.706,P<0.001,P<0.001);TG、Apo A1水平在两组间差异无统计学意义(Z=-1.577,Z=-0.408,P=0.115,P=0.683)。女性AD患者血清TG、CHO、LDL-C水平高于男性(Z=-2.737,Z=-3.963,Z=-4.417,P=0.006,P<0.001,P<0.001)。不同年龄组AD患者血清TG、CHO、HDL-C、LDL-C、Apo A1、Apo B差异均有统计学意义(Z=11.263,Z=10.060,Z=40.246,Z=10.451,Z=24.315,Z=19.922,P=0.010,P=0.018,P<0.001,P=0.015,P<0.001,P<0.001),血清CHO、LDL-C水平与年龄呈正相关(rs=0.160,rs=0.174,P=0.001,P<0.001),HDL-C、Apo A1、Apo B水平与年龄呈负相关(rs=-0.312,rs=-0.272,rs=-0.146,P<0.001,P<0.001,P=0.003),TG水平与年龄无相关性(rs=0.086,P=0.082)。AD患者中E2、E3及E4型各为3(3.33%)、43(47.78%)及44(48.89%)例,健康体检者中E2、E3及E4型各为22(12.72%)、117(67.63%)及34(19.65%)名,两组Apo E基因表现型分布情况差异具有统计学意义(χ^(2)=26.381,P<0.001),AD患者中Apo E4型是最常见的基因表现型,占48.89%(44/90),除了Apo A1(Z=7.821,P=0.020)外,TG、CHO、HDL-C、LDL-C、Apo B水平在Apo E2、E3和E4型患者之间差异无统计学意义(Z=3.732,Z=1.677,Z=1.455,Z=1.619,Z=2.202,P=0.155,P=0.432,P=0.483,P=0.445,P=0.333)。结论AD患者CHO、LDL-C水平降低,HDL-C、Apo B水平增高,患者血脂异常可能与年龄有关,可能与性别和Apo E基因型无相关性。

Objective To explore the correlation of serum lipids levels of Alzheimer′s disease(AD)patients with sex,age and apolipoprotein E(Apo E)gene polymorphism.Methods The retrospective study method was used,and 407 AD patients(142 males and 265 females,aged 52-91 years)were selected from Beijing Tiantan Hospital from January 2015 to August 2021 as the research target,and 894 healthy persons(339 males and 555 females,aged 52-94 years)who did body examination were selected as the control group.The AD patients were divided into four age groups according to the age interval of 10 years,including 85 aged 50-59 years,163 aged 60-69 years,119 aged 70-79 years,and 40 aged more than 80 years.The serum lipids levels were detected by biochemical analyzer,including triglycerides(TG),cholesterol(CHO),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),apolipoproteinA1(Apo A1)and apolipoprotein B(Apo B).ApoE gene polymorphism were detected by PCR fluorescent probe method.Mann-Whitney U test and Kruskal-Wallis H test were used to compare the serum lipids levels in each group.Results The levels of serum CHO and LDL-C were 3.30(1.41,4.82)mmol/L and 1.76(1.39,2.78)mmol/L in AD patients,and 4.84(4.24,5.56)mmol/L and 2.91(2.36,3.57)mmol/L in control group,and the levels of serum CHO and LDL-C of AD patients were significantly lower than control group(Z=-15.172,Z=-14.583,P<0.001,P<0.001).The levels of serum HDL-C and Apo B were 1.84(1.30,3.88)mmol/L and 1.17(0.85,1.57)g/L in AD patients,and 1.39(1.18,1.64)mmol/L and 0.93(0.81,1.09)g/L in control group,and the levels of serum HDL-C and Apo-B of AD patients were significantly higher than control group(Z=-12.249,Z=-9.706,P<0.001,P<0.001).There was no significant difference in TG and Apo A1 between 2 groups(Z=-1.577,Z=-0.408,P=0.115,P=0.683).The levels of TG,CHO,LDL-C in female AD patients were significantly higher than male patients(Z=-2.737,Z=-3.963,Z=-4.417,P=0.006,P<0.001,P<0.001).There were significant differences in TG,CHO,HDL-C,LDL-C,Apo A1 and Apo B among AD patients of all age groups(Z=11.263,Z=10.060,Z=40.246,Z=10.451,Z=24.315,Z=19.922,P=0.010,P=0.018,P<0.001,P=0.015,P<0.001,P<0.001).The serum CHO and LDL-C levels were positively correlated with age(rs=0.160,rs=0.174,P=0.001,P<0.001),and HDL-C,Apo A1 and Apo B levels were negatively correlated with age(rs=-0.312,rs=-0.272,rs=-0.146,P<0.001,P<0.001,P=0.003),and there was no correlation between TG level and age in AD patients(rs=0.086,P=0.082).There were 3 cases(3.33%)of E2,43 cases of E3(47.78%)and 44 cases of E4(48.89%)in AD patients,and 22 cases(12.72%)of E2,117 cases of E3(67.63%)and 34 cases of E4(19.65%)in control group.There was significant difference in Apo E genotype distribution between AD patients and control group(χ^(2)=26.381,P<0.001).Apo E4 was the most common genotype in AD patients,and the proportion was 48.89%.Except for Apo A1(Z=7.821,P=0.020),there was no significant difference in TG,CHO,HDL-C,LDL-C and Apo B levels among all patients with different genotypes(Z=3.732,Z=1.677,Z=1.455,Z=1.619,Z=2.202,P=0.155,P=0.432,P=0.483,P=0.445,P=0.333).Conclusion The levels of CHO and LDL-C decreased while the levels of HDL-C and Apo B increased in AD patients.The dyslipidemia in AD patients might be correlated with age,but not sex and Apo E genotypes.