| BackgroundAlzheimer's disease(AD)is the most common cause of dementia,the etiology and pathogenesis is not yet clear,and effective therapy is clinically lacking.The development of AD may be the result of environmental and genetic factors,with genetic contribution of 80%.Therefore,gene detection plays an important role in the etiology of AD.Understanding the potential genes associated with AD is of great help for further clinical molecular diagnosis.Apolipoprotein E(ApoE)gene is recognized worldwide as a gene related to AD.In addition,it is also believed that the metabolism of alcohol may be related to the pathogenesis of AD,and alcohol dehydrogenase(ADH)and aldehyde dehydrogenase(ALDH)are the key enzymes in the process of alcohol metabolism.Polymorphisms of ADH and ALDH genes have been shown to be associated with the susceptibility to a variety of neurodegenerative diseases,but conclusions are inconsistent in different regions and races.Inner Mongolia Autonomous Region is located in the north of China,where more Mongolians and Han people live.Compared with other ethnic groups,the Han people in Inner Mongolia have different genetic background,which may be different in the etiology and molecular pathology of AD.The climate in Inner Mongolia is cold,and the Han people in Inner Mongolia have different living and eating habits,who take more alcohol.Therefore,it is of great significance to study the ADH and ALDH gene polymorphisms of AD in different races and populations.Objective[1]To verify the association between ApoE gene polymorphisms and sporadic Alzheimer's disease(sAD)through detecting ApoE gene expression of Han population in Inner Mongolia.[2]To understand the association between ADH1B rs1229984 and sAD by detecting the ADH1B rs1229984 gene polymorphism of Han population in Inner Mongolia;to investigate whether the population of ADH1B rs1229984 with AD positive family history and alcohol intake being related to development of AD.[3]To understand the association between ALDH2 rs671 and sAD by detecting the ALDH2 rs671 gene polymorphism of Han population in Inner Mongolia;to investigate whether the population of ALDH2 rs671 with AD positive family history and alcohol intake being related to development of AD,Methods[1]From March 2015 to October 2017,outpatients and inpatients of Han nationality with sAD in the Affiliated Hospital of Inner Mongolia Medical University,as well as some community patients with sAD in collaboration with the hospital,were selected as the case group,and healthy people in the community were recruited as the control group.The data including emographic,past medical history,personal history and family history,as well as alcohol intake,were registered.[2]The genomic DNA of ApoE,ADH1B and ALDH2 was extracted from whole blood samples,and the concentration and purity of DNA were determined.Genotypes,gene amplification and electrophoresis were detected.For ADH1B and ALDH2,the candidate single nucleotide polymorphism(SNP)was searched.The distribution of gene frequency was detected by Hardy-weinberg equilibrium.[3]In order to compare the differences between case group and control group,t test was used to anlalyze demographic and clinical variables;?2 test,genotype and allele frequency;ratio ratio(OR)and 95%confidence interval(CI)of each gene polymorphism locus,the correlation strength.Logistic regression model was used to analyze the correlation of sAD risk among different genotypes of gene polymorphisms,and Spearman correlation coefficient was used to analyze the correlation of increased risk of AD among ADH1B rs1229984,ALDH2 rs671,AD positive family history and alcohol intake in Han population who live in Inner Mongolia.Results[1]A total of 503 sAD patients and 384 controls were recruited.In the case group,the educational level was lower(P = 0.045),the proportion of AD positive family history and alcohol intake was higher(P<0.05),and there was no significant difference in sex composition,average age,smoking,hypertension,diabetes and stroke between the two groups(P>0.05).[2]Both in case and control groups,the gene frequency distribution of gene polymorphisms in ApoE rs429358 and rs7421,ADH 1B rsl229984 and ADH 2rs671 conformed to Hardy-Weinberg equilibrium law,which indicated that the SNP population was well represented.[3]Both in case and control groups,the distribution frequencies of ApoE epsilon 2,3 and 4 alleles were different(?2 = 66.290,P = 0.000),in which the frequencies of epsilon 3 were the highest(?2 = 73.355,P = 0.000),and the six genotypes of alleles were different(?2 = 73.355,P = 0.000).The frequency of ApoE epsilon 4(+)in case group was higher than that in control group(?2 = 67.283,P = 0.000),ApoE epsilon 4 increased the risk of sAD(OR 4.20,95%CI 2.93?6.00).[4]In the Han population of Inner Mongolia,the distribution frequency of ADH1B rs 1229984 genotype(?2 = 7.136,P = 0.028)and allele(?2 = 4.308,P = 0.038)were different;allele A increased the risk of sAD(OR 1.24,95%CI 1.01-1.53).After the ApoE epsilon 4 was stratified,for epsilon 4(+)subgroup,the distribution of the genotype was different(?2 = 8.484,P = 0.014),and the allele distribution was not different between the case and the control group.[5]In the Han population of Inner Mongolia,the distribution frequency of ALDH2 rs671 genotype(?2 = 14.662,P = 0.001)and allele(?2=12.092,P = 0.001)were different;allele A increased the risk of sAD(OR 1.43,95%CI 1.17?1.75).After the ApoE epsilon 4 was stratified,for epsilon 4(+)subgroup,both the distribution of the genotype(?2 = 6.185,P = 0.045)and the allele(?2 = 5.430,P=0.02)were different;distribution was not different between the case and the control group;for epsilon 4(-)subgroup,both the distribution of the genotype(?2= 10.789,P = 0.005)and the allele(?2 = 7.909,P = 0.005)were also different.[6]Among the three genotypes of GG,GA and AA both in ADH 1B rs 1229984(OR 2.54,95%CI 1.19-5.41)and ADH rs671(OR 4.57,95%CI 1.60-14.01),the distribution of AA in the case group was significantly higher than that in the control group.In ADH1B and ALDH,the OR values of GG/GA+AA were 1.78 and 1.79,95%CI were 1.09-2.93 and 1.08-2.97,respectively;the OR values of GG+GA/AA were 2.33 and 4.17,and 95%CI were 1.18-4.47 and 1.49-12.67 respectively,suggesting that both models were associated with increased risk of sAD in Han population of Inner Mongolian.[7]Spearman correlation coefficient analysis showed that both ADH1B rsl229984 and ALDH rs671 with AD positive family history and alcohol intake increased the risk of sAD(P<0.05).Conclusion[1]In the Han population of Inner Mongolia,ApoE gene is associated with the onset of sAD;ApoE epsilon 4 may increase the risk of sAD.[2]In the Han population of Inner Mongolia,the ADH1B rs1229984 gene locus is significantly associated with the risk of sAD;the ApoE gene may increase the role of ADH1B gene in sAD;the AA genotype of ADH1B rs1229984 gene locus may increase the risk of sAD;both dominant and recessive models are associated with increasing the risk of sAD;the risk of sAD increases with AD positive family history and alcohol intake.[3]In the Han population of Inner Mongolia,the ALDH2 rs671 locus is significantly associated with the risk of sAD;ApoE gene may increase the role of ALDH2 gene in the development of sAD.The AA genotype at the ALDH2 rs671 locus may increase the risk of sAD.Both dominant and recessive models are associated with increased risk of sAD,and the association of ALDH2 rs671 with AD positive family history and alcohol intake increases the risk of sAD. |
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