Study On The Correlation Between Blood Glucose And KCNQ1 Gene Among Elderly People In A County Of Guangxi

BackgroundDonglan county,hechi city,guangxi province is the "hometown of longevity" in China.Recently,we conducted genome-wide association analysis(GWAS)on the blood glucose phenotypes of 1040 elderly people in rural Donglan County,and found that KCNQ1 gene might be related to the glucose metabolism level of this population.Diabetes not only affects the daily living ability of patients,but also seriously affects the life span of patients.As a quantitative trait that was closely related to type Ⅱ diabetes,blood glucose levels are complicated in the regulation of human body,and the level of variation is the result of many environmental factors and genetic factors.Epigenetics,as a bridge between genotype and phenotype,is the phenomenon of changing the final result of a locus or chromosome without changing the underlying DNA sequence.DNA methylation is the most characteristic epigenetic modification.Although the epigenome is known to be regulated by the environment,this regulation may also be affected by genetic variation.Therefore,based on previous work,this study intends to explore the influencing factors of abnormal glucose metabolism among elderly population in Donglan County,to investigate the polymorphism of KCNQ1 gene among the elderly population in this region from a genetic perspective,to explore the methylation level of the promoter region of this gene from the perspective of epigenetics,and for the possible relationship between these factors and abnormal glucose metabolism,so as to provide a scientific basis for the next study of the relationship between genetics and blood glucose.PART ⅠANALYSIS OF ABNORMAL GLUCOSE METABOLISM STATUS AND ITS INFLUENCING FACTORS AMONG ELDERLY POPULATION IN A COUNTY OF GUANGXIObjective:To understand the abnormal situation of glucose metabolism and its influencing factors among rural elderly population in a county of Guangxi.Methods:Through the cross-sectional survey method,a survey was conducted on the elderly aged 60 and over in three townships in a county of Hechi City,Guangxi.The Epidata epidemiological softwarewas used to create a database and double-entry the baseline data.Multivariate analysis was performed using SPSS22.0 statistical software.Results:1.A total of 4355 elderly people participated in the survey,in which the total abnormal rate of glucose metabolism was 16.1%(699/4355),3656 in the normal group,and 699 in the abnormal group.Among them,male:female=1:1.48;the highest proportion was 60-69 years old population,it accounted for 53.7%(2337/4355).The statistically significant differences between the normal group and the abnormal group were gender,education level,ethnicity,doing farm work and drinking(P<0.05).The specific values of the above factors in the abnormal group and the normal group were:women accounted for 51.2%(358/699)and 61.3%(2240/3656),respectively;the education level was the highest in illiteracy,accounting for 21.7%(152/699)and 47.2%(1725/3656);Zhuang also accounted for the highest proportion,accounting for 82.3%(575/699)and 85.8%(3137/3656)respectively;doing farm work accounted for 57.9%(405/699)and 65.7%(2402/3656)respectively;drinkers accounted for 32.5%(227/699)and 22.9%(837/3656)respectively.2.Dietary habits:the proportion of cooking in the abnormal sugar regulation group was higher than that in the normal group,which was 19.7%(138/699)and 16.1%(589/3656),respectively.The proportion of cooking in the abnormal group using animal oil was lower than that in the normal group,which was 86.6%(605/699)and 89.9%(3285/3656),respectively.The proportion of vegetables consumed per day was higher than that inthe normal group,which was 74.7%(522/699)and 69.6%(2545/3656),respectively.The above factors were statistically different between the two groups(P<0.05).3.Related clinical indexs:Systolic blood pressure(SBP),diastolic blood pressure(DBP),triglyceride(TG),uric acid(UA),creatinine(Cr)and BMI in the group with abnormal glucose metabolism were all higher than those in the normal group.The proportion of abdominal obesity reflected by waist-to-hip ratio(WHR),and the proportion of osteoporosis reflected by bone density(BMD)were also higher than that of normal group.The above factors were statistically significant between the two groups.In the abnormal group and the normal group,SBP was 143.80±23.83 mmHg and 140.09±22.65 mmHg,DBP was 82.32±14.04 mmHg and 80.17±13.15 mmHg,respectively;and TG was 1.22(0.78)mmol/L and 1.03(0.74)mmol/L respectively;UA was 3 55.16±126.10μmol/L and 320.62±113.91μmol/L,Cr was 70.33±29.73μmol/L and 67.66±24.92pmol/L,respectively;and the proportion of overweight or obesity reflected by BMI index was 31.8%(222/699)and 22.6%(827/3656),WHR reflected the proportion of abdominal obesity in 49.5%(346/699)and 42.5%(1553/3656).The proportion of osteoporosis was 25.6%(177/699)and 23.3%(852/3656)respectively.4.Unconditional logistic regression analysis was used to investigate the influencing factors of abnormal glucose metabolism.The results of multivariate analysis showed that non-farm workers were 1.259 times more likely to have abnormal glucose metabolism than farm workers(OR=1.259,95%CI=1.057～1.499).Those with TG≥1.7mmol/L were 1.185 times more likely to have abnormal glucose metabolism than those with TG<1.7mmol/L(OR=1.185,95%CI=1.108～1.268).Those with hyperuricemia were 1.034 times more likely to have abnormal glucose metabolism than those with normal uric acid(OR=1.034,95%CI=1.007～1.662).Those with BMI>24kg/m2 were 1.056 times more likely to have abnormal glucose metabolism than those with BMI<24kg/m2(OR=1.056,95%CI=1.026～1.087).Conclusions:Working,TG,UA and BMI are possible influencing factors of abnormal glucose metabolism in elderly people aged 60 and over in a county of Guangxi.PART ⅡCORRELATION BETWEEN KCNQ1GENE POLYMORPHISM AND ABNORMAL GLUCOSE METABOLISM AMONG ELDERLY POPULATION IN A COUNTY OF GUANGXIObjective:To understand the distribution of KCNQ1 gene polymorphism in rural elderly population of Guangxi,and to explore the possible relationship between genetic polymorphism andabnormal glucose metabolism.Methods:The multi-SNP typing kit imLDRTM was used to genotype the 6 SNP loci of KCNQ1 gene in 4355 samples of rural population aged 60 years and above in a county of Guangxi.Combined with epidemiological data(baseline questionnaire and physical examination results)and genotyping results,GMDR0.9 software and SPSS22.0 software were used for statistical analysis.Results:1.Fasting glucose levels:there were 3656 people in the normal glucose metabolism group(fasting blood glucose<5.6mmol/L),and 699 people in the abnormal group(fasting bloodglucose>5.6mmol/L).The fasting blood glucose level in the abnormal group was higher than the normal group(P<0.05).2.Polymorphism distribution characteristics2.1 Hardy-Weinberg equilibrium test for KCNQ1 gene was performed in all the 6 SNP sites of the study population(P>0.05).2.2 In the normal and abnormal groups of all populations,the distribution of rs151290,rs 163184,and rs2237897 in the three genotypes was statistically significant(P<0.05).The differences in theallele frequencies between the four loci rs151290,rs163184,rs2237892,and rs2237897 were statistically significant(P<0.05).In the Zhuang population,the distribution of genotypes between the three loci rs 151290,rs163184 and rs2237897 was statistically significant(P<0.05).The differences in the allele frequencies between the five loci rs1057128,rs151290,rs163184,rs2237892,and rs2237897 were statistically significant(P<0.05).2.3 Correlation analysis between different genotypes and abnormal glucose metabolism Among all participants,carriers of AA genotype and A allele(AA+AC)at rs151290 were 0.704 times(0.543～0.912)and 0.822 times(0.696～0.971)more likely to have abnormal glucose metabolism than carriers of CC genotype,respectively.Those with T allele(CT+TT)at rs2237892 were 0.848 times more likely to have abnormal glucose metabolism than those with CC genotype(0.721～0.998).Carriers of the rs2237897 CTgenotype,TT genotypeand T alleles(CT+TT)were 0.791 times(0.666～0.938),0.737 times(0.549～0.989)and 0.780 times(0.663～0.918)more likely to have abnormal glucose metabolism than CC genotypecarriers.2.4 Relationship between KCNQ1 gene-environment interaction and abnormal glucose metabolism:The results of MDR method showed that the optimal interaction model was a three-factor model composed of wok,TG and rs2237897.In all and zhuang population,the interaction analysis of rs151290,rs1057128,rs163184,rs223797 and rs2313162 showed that the mutation of rs151290 could reduce the risk of fasting glucose abnormality(P<0.05).Whenrs2237897 interacts with rs1057128,rs151290,rs223792 and rs2313162,mutation of rs2237897 could reduce the risk of abnormal fasting glucose(P<0.05).2.5 Relationship between KCNQ1 gene polymorphism and serum lipid levelAmong all participants,in the group with normal glucose metabolism,both TC and HDL-c level of alleleA carrier(AG+AA)were lower than those of GG genotype at rs1057128(P<0.05).In the normal glucose metabolism group of all participants,compared with CC genotype,HDL-c levels in AC genotype carriers were lower(P<0.05),and TC,HDL-c and LDL-c levels in A allele(AG+GG)carriers were lower at rs151290(P<0.05).In the Han population with normal glucose metabolism,the LDL-c level of the variant G allele carrier(GT+GG)at loci rs163184 was significantly higher than that of TT genotype(P<0.05).Conclusions:1.The polymorphisms of KCNQ1 loci rs151290,rs2237892 and rs2237897 may be associated with the risk of abnormal glucose metabolism among rural elderly in a county of Guangxi.2.The interaction amongdoing farm work,TG and loci rs2237897 had the greatest impact on the abnormal glucose metabolism of rural elderly in a county of Guangxi.The variation of rs1057128,rs151290 and rs2237897 might reduce the risk of abnormal glucose metabolism.3.Interacting with six SNP loci,respectively,farming factors mightreduce the risk of abnormal glucose metabolism,while high BMI and TG might increase the risk of abnormal glucose metabolism.4.The polymorphism of KCNQ1 loci rs1057128,rs151290,rs 163184 and rs231362 might be related to the different blood lipid indexes of local population.PART Ⅲ ASSOCIATION BETWEEN METHYLATION LEVEL OF KCNQ1 GENE AND ABNORMAL GLUCOSE METABOLISM IN ELDERLY POPULATION IN A COUNTY OF GUANGXIObjective:To understand the correlation between KCNQ1 gene methylation and abnormal glucose metabolism,and to explore the relationship between KCNQl gene 6 SNP loci and 23 CpG loci in gene promoter region.Methods:The methylation levels of 23 promoter regions of KCNQ1 gene were determined by bisulfite amplification sequencing technology.Multiple linear regression was used to analyze the relationship between the methylation rate of 23 CpG sites and abnormal glucose metabolism.Matrix eQTL method was used to analyze the relationship between 6 SNP variation loci of KCNQ1 gene and 23 CpG loci in its promoter region.Results:1.A total of 193 people were included in this part of the study,including 96 in the normal glucose metabolism group and 97 in the abnormal group.There were no statistically significant differences in demographic characteristics,dietary habits and relevant clinical indicators between the two groups(P>0.05).2.Multiple stepwise regression analysis showed that in the CpG locus that affected glucose metabolism abnormality in the elderly,the positions of its effect from high to low-were 66,113,138(P<0.05).3.There were statistically significant differences in methylation levels at CpG site 151 in the promoter region between carriers of different genotypes of KCNQ1 SNP loci rs2237892 and rs2237897(P<0.05).The methylation level of different genotypes of rs 163184 carriers at CpG locus 40 and 80 in the promoter region were statistically significant(P<0.05).Conclusions:1.The methylation levels of CpG loci 66,113 and 138 of KCNQ1 gene might be related to the glucose metabolism of the elderly in a county of Guangxi.2.The polymorphism of rs2237897 in intron 15 of KCNQ1 gene might be related to the methylation level of CpG site 151 in the promoter region of KCNQ1 gene.