| Objective:.To explore transformation of environmental risk factors of mild cognitive impairment(MCI)in the elderly in Xinjiang,this study analyzed the trends of MCI in the elderly communities in Urumqi Xinjiang from 2014 to 2018.To explore the genetics and epigenetics factors of MCI,nine genes' single nucleotide polymorphism(SNP)loci(APOE,MAPT,PLAU,OGG1,A2 M,MME,SIRT1,GSK3 B,HMGCR)were studied between MCI group and control gourp and assoiations between DNA methylation of APOE,PLAU,A2 M and MCI were analyzed,and further the interactions were analyzed between these three genes' SNP loci and DNA methylation.Methods:(1)Part I: The method of stratified randomized cluster sampling was adopted in epidemiological surveyes,and on-site and household surveys were adopted.(2)Part II: Case-control research method was used in this Part,and 106 MCI patients and 136 normal controls were recruited according to the diagnostic and exclusion criteria.The PCR reaction and Sanger sequencing were used to complete genes typing.(3)Part III:Case-control research method was used in this Part,and 43 MCI patients and 125 normal controls were recruited according to the diagnostic and exclusion criteria.DNA methylation was performed using quantitative methylation-specific PCR Determination.Results:(1)Part I:(1)In 2014,the prevalence of MCI in the elderly communities in Urumqi was 8.404%,and the standardized prevalence was 7.144%;the prevalence of males was 6.970%,and the standardized prevalence was 4.308%;The prevalence of females was 9.677%,and thestandardized prevalence was 8.550%.The standardized prevalence of females was significantly higher than that of males(P < 0.05).(2)In 2014,the prevalence of MCI in the elderly communities in Urumqi increased significantly with age,and decreased significantly with the advance of education;the prevalence of MCI increased significantly with age among males,and decreased significantly with advance of education among females.The prevalence of MCI in females is significantly higher than that of males in illiterate people.The prevalence of MCI is significantly higher in people with high TG(all P values <0.05).(3)Logistic regression analysis showed that female,hypertriglyceridemia,and age increase were independent risk factors for MCI prevalence in the elderly communities in Urumqi in 2014,and the advance of educational level was a protective factor(all P values < 0.05).(4)In 2018,the prevalence of MCI in the elderly communities in Urumqi was 10.339%,and the standardized prevalence was 9.780%;the prevalence of males was 9.406%,the standardized prevalence was 7.981%;the prevalence of females was 10.864%,and the standardized prevalence was 11.528%.There was no significant difference between males and females(P > 0.05).(5)In 2018,the prevalence of MCI in the elderly communities in Urumqi increased significantly with age;the prevalence of MCI increased significantly with age among females and increased significantly in people with high TC(all P values < 0.05).(6)Logistic regression analysis showed that high TC and age increase were independent risk factors for MCI in the elderly communities in Urumqi in 2018.(7)The prevalence of MCI in 2018 was higher than that in 2014,but the difference was not statistically differently(P > 0.05);the prevalence of MCI in the elderly aged 80 to 89 years old was significantly higher than that in 2014,and the prevalence of MCI in primary school education and in high TC increased significantly compared to 2014(all P values < 0.05).(2)Part II:(1)The polymorphisms of APOE rs7412 rs429358 had significant differences between MCI group and control group in Han people,and?4/?4 genotype was significantly increased in MCI group(both P values < 0.05).There were no significant differences in Uygurs and the total population(P >0.05).(2)The polymorphisms of GSK3 B rs6438552 had significant differences between MCI group and control group in total population,Han and Uygur population(all P values < 0.05),and in non-APOE ?4 carriers,the genotype and allele frequencies were also significantly different between MCI group andcontrol group(P < 0.05).(3)The MME rs3736187 polymorphisms had significant differences between MCI group and control group in males(P < 0.05).(4)The polymorphisms of MAPT rs242557 had significant differences between MCI group and control group in Uygur females(P < 0.05).(5)HMGCR rs3846662 polymorphisms had significant differences between MCI group and control group in non-APOE ?4 carriers(P < 0.05).(6)The polymorphisms of OGG1rs1052133 had significant differences between MCI group and control group in Han males(P < 0.05).(7)SIRT1 rs7895833 polymorphisms had significant differences between MCI group and control group in APOE ?4 carriers in Uygurs(P < 0.05).(8)PLAU rs22275564 and A2 M rs669 polymorphisms didn't have significant differences between MCI group and control group in total population,Han population and Uygur population(all P values > 0.05).(3)Part III:(1)APOE gene methylation levels were significantly different between MCI group and control group in Uygur population;In males and non-APOE ?4 carriers,there were significant differences between MCI group and control group(both P values < 0.05).(2)There was no significant difference of PLAU methylation levels between MCI group and control group in Uygur population(P > 0.05);In males,the methylation levels of PLAU were significantly lower in MCI group than in control group,and PLAU methylation levels were significantly lower in the male MCI group than in the female MCI group(both P values < 0.05);In the PLAU rs2227564-CC genotype carriers,PLAU methylation levels were significantly different in MCI group than in control group;In males and PLAU rs2227564-CT genotype carriers,PLAU methylation levels were significantly different in MCI than in control group(both P values < 0.05).(3)There was no significant difference of methylation levels of A2 M promoter region between MCI group and control group.No difference was found in the distribution of A2 M methylation levels between MCI group and control group(both P values >0.05).(4)Interaction analysis showed that there was an interaction between PLAU rs2227564,APOE rs7412 rs429358,gender,and APOE methylation,which was related to Uygur's MCI(P <0.05).(5)In the correlation analysis,all clinical indicators had no correlation with APOE methylation(P > 0.05);In the female MCI group,the methylation levels of PLAU gene promoter region were significantly negatively correlated with TG(r =-0.472,P = 0.031);There was a negative correlation between the A2 M methylation and LDL-C in the malecontrol group(r =-0.294,P = 0.020).Conclusion:(1)Part I:(1)From 2014 to 2018,the prevalence of MCI in elderly people aged 60 and above in Urumqi communities showed an upward trend.(2)The prevalence of MCI in the elderly aged 80 years and above,especially women,shows a rapid increase.(3)The protection of low education(primary and below)to MCI is unstable,while the protection of secondary and higher education(junior high school,high school and above)to MCI is stable.(4)Over time,age and abnormal lipid metabolism is an independent risk factor for MCI in the elderly communities in Urumqi from 2014 to 2018.(2)Part II:(1)GSK3B rs6438552 polymorphism is independent of APOE ?4 and is related to MCI in the elderly in Xinjiang,and it is related to MCI in both Han and Uygur population.(2)The genes which are related to MCI and the distribution is different in Han and Uygur population in Xinjiang include APOE,MAPT,OGG1,and SIRT1.(3)The gene which is related to MCI and the distribution is different in gender is MME.(4)The genes which are related to MCI and are independent of APOE ?4 in Xinjiang elderly include GSK3 B and HMGCR;The gene which is related to MCI and are cooperate with APOE ?4 is SIRT.(3)Part III:(1)The high methylation levels of APOE are related to MCI in Xinjiang Uygur elderly,and this correlation is more obvious in Uygur males.(2)The low methylation levels of PLAU promoter region are significantly related to MCI in Xinjiang Uygur males.(3)The levels of methylation in the promoter region of A2 M have no association with MCI in Xinjiang Uygur elderly.(4)PLAU gene rs2227564 interacts with APOE rs7412 rs429358,gender and APOE methylation level,which is a risk factor for the development of MCI in Xinjiang Uygur elderly. |
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