Interaction Of Aluminum Exposure And ApoE?4 Gene On Cognitive Functions And ApoER2 Protein Expression Of Workers

Objective:To explore the interaction of aluminum exposure and ApoE?4 gene on cognitive functions and ApoER2 protein expression of workers,using occupational epidemiological survey.Methods:A total of 1121 in-service workers in a large aluminum factory were investigated in Shanxi Province.General information was collected using a self-designed questionnaire.Cognitive functions were assessed by the Mini-mental State Examination?MMSE?,the clock-drawing test?CDT?,the Digit Span Test?DST,including DSFT and DSBT?,the fuld object memory evaluation?FOM?,and the verbal fluency task?VFT?.The plasma-Al mass concentrations were measured by inductively coupled plasma-mass spectrometry?ICP-MS?as an internal exposure indicator,and the participants were divided into four Al exposure groups according to the quartile of plasma-Al concentrations,namely Q1,Q2,Q3,and Q4.ApoE genotype was determined by Ligase Detection Reaction?LDR?,and the content of ApoER2?LRP8?protein in plasma was determined by ELISA.The multiplicative model was fitted using non-conditional logistic regression and additive model was fitted using crossover analysis to analyze the interaction between plasma-Al concentration levels and the ApoE?4gene.Results:1.The average level of plasma-Al concentrations was 21.76?10.56,46.67??g/L.The subjects were divided into four subgroups based on the quartile of plasma-Al concentrations named as Q1?<10.56?g/L?,Q2?10.56-21.76?g/L?,Q3?21.76-46.67?g/L?,and Q4??46.67?g/L?subgroups,respectively.2.The crude comparisons of general information and cognitive functions showed that there were no significant differences among the four groups with regards to age,marriage status,education level,economic income,and habits of smoking?all P>0.05?.While duration and type of work,habits of drinking showed significant differences?all P<0.05?.And there were significant differences among the four groups with regards to the sores of CDT,DST,DSFT and DSBT?all P<0.05?,however,the sores of MMSE,FOM,and VFT showed no significant differences?all P>0.05?.3.The relationship between plasma-Al concentrations and cognitive functions:?1?The adjusted association between influential factors and cognitive functions showed that age,smoking and plasma-Al concentrations may be risk factors for cognitive impairment?all P<0.05?,and higher education level,as well as higher economic income may be protective factors for cognitive impairment?all P<0.05?.However,the relationship between type of work and cognitive function performance was uncertain,for that electrolytic workers performed worse on MMSE,CDT,DST,and DSFT?all P<0.05?,but better on FOM??=0.665,P=0.001?,compared with non-electrolytic workers.?2?The test of trend using general linear model and logistic regression analysis showed dose-response relationships between plasma-Al levels and the performances of CDT,DST,and DSBT(all P_trend<0.05),after adjusting for age,marriage status,education level,economic income,type of work,smoking and drinking.As plasma-Al levels increased,the performances of CDT,DST,and DSBT were worse,and the risk of cognitive impairment was increasing.4.The relationship between ApoE gene polymorphism and cognitive function:?1?Hardy-weinberg balance test showed that ApoE genotype frequencies of the total study participants,cognitive impairment group and normal cognitive function group were all in line with H-W genetic equilibrium??²=2.019,P=0.846;?²=1.934,P=0.858;?²=1.621,P=0.993?.?2?The?4/?4 genotype was not detected in normal cognitive function group.And the frequencies of?3/?3 genotype were much lower,but?3/?4 genotype were significantly higher in cognitive impairment group than in normal cognitive function group??²=27.072,P<0.001?.The frequencies of?2,?3,and?4 alleles in cognitive impairment group with 5.9%,80.4%,and 13.7%,respectively,were significantly different with that in normal cognitive function group with 7.4%,86.8%,and 5.8%,respectively??²=12.321,P=0.002?.The frequency of?3+gene in cognitive impairment group was significantly lower than that in normal cognitive function group,while the frequency of?4+gene was much higher than that in normal cognitive function group??²=25.358,P<0.001?.?3?After adjusting for confounders,?3/?4 increased the risk of cognitive impairment?OR=2.467,95%CI:1.579-3.857?,compared to those individuals with?3/?3 genotype.And individuals with?4+genotype had adjusted ORs of 2.463?95%CI:1.577-3.846?,compared with?3+genotype.5.There was an additive interaction between plasma-Al concentration levels and ApoE?4 gene?RERI=2.355,AP=0.442,S=2.190?.The group of high aluminum exposure,?4?+?has the highest risk of cognitive impairment?OR=5.228,95%CI:2.945-9.281?of all groups.Cognitive impairment caused by interaction of plasma-Al concentration levels with ApoE?4 gene in all cognitive impaired individuals accounted for 44.2%?AP=0.442,95%CI:0.076-0.808?.6.After adjusting for confounders,there was a negative correlation of plasma-Al concentrations??=-0.067,P=0.010?and?4?+???=-0.087,P=0.003?with the content of ApoER2?LRP8?protein expression.And the content of ApoER2?LRP8?protein expression in the group to high aluminum exposure,?4?+?was the lowest,but in the group to low aluminum exposure,?4?-?was the highest?P<0.001?.Conclusion:1.There is a dose-response relationship between aluminum exposure and cognitive impairment.As aluminum exposure levels increased,the cognitive functions were gradually worse,and the risk of cognitive impairment was gradually increasing.The ApoE?4 gene may be a risk factor for cognitive impairment,but the relationship between ApoE?2 gene and cognitive impairment was not found in this study.2.There is an additive interaction between aluminum exposure and ApoE?4 gene.When the two factors act together,the risk of cognitive impairment may be increased,and 44.2%of the risk can be attributed to the interaction of the two factors.3.Both aluminum exposure and ApoE?4 gene can decrease the expression of ApoER2?LRP8?protein,and the interaction of the two factors may further decrease the expression of ApoER2?LRP8?protein.