| Objective: Diabetes Mellitus(DM)is a systemic chronic metabolic disease characterized by insulin resistance and(or)impaired islet cell function.The prevalence of diabetes mellitus is increasing year by year all over the world.Type 2 diabetes Mellitus(T2DM)is the main type of diabetes in China.The awareness rate,treatment rate and control rate of patients are low,cardiovascular disease,retinopathy,diabetic nephropathy,neuropathy,diabetic foot,and other life-threatening complications can occur.T2 DM and its complications not only do great harm to patient’s health,but also bring huge economic burden to families and society.The occurrence of T2 DM is the result of the interaction of genetic factors and environmental factors.More and more research evidences show that genetic factors play an important role in the occurrence and development of T2 DM,however,the exact molecular mechanism of T2 DM has not been fully elucidated,so the exact mechanism of genetic factors in T2 DM needs to be further explored.Long non-coding RNA(LncRNA)is a group of RNAS with length greater than 200 base units,which can’t encode proteins.LncRNA is tissue-specific and space-time specific.According to statistics,non-coding RNA accounts for more than 70% of the human genome.Single Nucleotide Single-Nucleotide Polymorphism(SNP),a Single base substitution in DNA sequence,is the most common type of variation in the genome,with one SNP for every 1000 bases.Human Genome 9p21 has been found to be associated with cardiovascular disease,and the CDKN2B-AS1 polymorphism is involved in the development of coronary heart disease by mediating an inflammatory signal response,rs10965215 and rs10738605 were found to be associated with the risk of coronary heart disease in Chinese Han population.SNP IN LncRNA is also reported to be a risk gene for diabetes susceptibility and prognosis,but no association has been found in clinical studies.Basic research shows that LncRNA plays an important role in the development of T2 DM by participating in the maintenance of cell function and the conduction of insulin signal.Therefore,this study intends to explore the association between LncRNA CDKN2B-AS1SINGLE-NUCLEOTIDE POLYMORPHISM(rs10965215,rs10738605)and susceptibility to T2 DM.The association between Lnc NCRNA CDKN2B-AS1 SNPs(rs10965215,rs10738605)and cardiac damage in patients with T2 DM was investigated.Methods:Methods: 1.5ml fasting venous blood was collected from all subjects.Genomic DNA was extracted from all blood samples by phenol-chloroform method.T test and chi square test were used to compare continuous variables and categorical variables between two groups.Logistic regression model was used to calculate OR and its 95% confidence interval to estimate the association between different genotypes at different SNP sites and the risk of T2 DM.Further stratified analysis was conducted according to gender,age,alcohol consumption and other factors,and the correlation between the interaction between genes and environment and the risk of T2 DM was explored.Multivariate logistic regression analysis was used to analyze the relationship between SNP-SNP genotype interactions and susceptibility to T2 DM.2.GE Vivid E9 color doppler ultrasound diagnostic instrument,M5 S probe,frequency 1.0-5.0mhz were used to collect the para-sternal left ventricular long axis section,fourchamber cardiac apex view,three-chamber cardiac apex view,and two-chamber cardiac apex view.Then the post-processing workstation equipped with Echo Pac offline analysis software is used for image data analysis.Get all the subjects’ heart rate(HR),surface area(BSA),left ventricular end-diastolic Canon(LVEDD),left ventricular end systolic Canon(LVESD),left atrial volume index(LAVI),left ventricular isovolumetric diastolic time(IVRT),mitral valve orifice early diastolic blood flow velocity(E),mitral valve mouth late diastolic blood flow velocity(A),interval of mitral valve ring early diastolic velocity(Sept E ’),sidewall mitral valve ring early diastolic velocity(Lat E ’),left ventricular ejection fraction(LVEF),left ventricular peak strain overall longitudinal data(GLS),etc.The mean standard deviation is used if the measurement data conforms to the normal distribution,and the median and interquartile distance m are used if the measurement data conforms to the non-normal distribution.The result of the count data is expressed as a percentage.The ultrasonic parameters of LncRNA CDKN2B-AS1 Single-nucleotide polymorphism rs10965215,rs10738605 were compared with control group and case group by independent sample t test,and the ultrasonic parameters were compared with univariate variance analysis.Results:1.Relationship between LncRNA CDKN2B-AS1 SNP rs10965215,rs10738605 and susceptibility to T2DMCompared with CDKN2B-AS1 rs10965215 wild AA carriers,AG carriers had a reduced risk of developing T2DM(OR = 0.712,95%CI = 0.509-0.994,P = 0.046).The dominant gene model showed that compared with wild AA carriers,individuals with AG+GG genotypes had a lower risk of developing T2DM(OR = 0.692,95%CI = 0.505-0.948,P =0.022).Compared with A allele carriers,G allele carriers had A lower risk of developing T2DM(OR = 0.721,95%CI = 0.565-0.920,P = 0.008).Compared with individuals carrying the wild allele G of LncRNA cdkn2a-as1 rs10738605,the risk of T2 DM was reduced in the mutant allele C carriers(OR = 0.742,95%CI = 0.582-0.948,P = 0.017).2.Relationship between LncRNA CDKN2B-AS1 SNP rs10965215,rs10738605 and susceptibility to T2DM(stratified analysis)After adjusting for age,gender and other confounding factors,the risk of developing T2 DM was reduced in non-drinkers compared with wild AA genotype carriers in CDKN2B-AS1 single nucleic acid polymorphism rs10965215 AG genotype(OR = 0.667,95%CI = 0.459-0.971,P = 0.035).In the dominant model,individuals with AG+GG genotype had a reduced risk of T2 DM compared with those with the wild AA genotype(OR = 0.655,95% CI = 0.460-0.933,P = 0.019).After adjusting for gender,alcohol consumption and other confounding factors,compared with CDKN2B-AS1 single nucleoprotein polymorphism rs10738605 GC+GG genotype carriers,the risk of T2 DM was reduced in patients with mutant CC genotype(OR = 0.717,95%CI = 0.526-0.978,P= 0.036).3.Interaction between LncRNA CDKN2B-AS1 single nucleotide polymorphism rs10965215,rs10738605 and susceptibility to T2DMThere was no significant interaction between genotype rs10965215 and genotype rs10738605 of LncRNA CDKN2B-AS1 Single-nucleotide polymorphism.4.Correlation between LncRNA CDKN2B-AS1 single nucleotide polymorphism and environmental risk factors and susceptibility to T2DMThe genotype AG of LncRNA CDKN2B-AS1 Mutant Single-nucleotide polymorphism rs10965215 interacts with non-alcohol exposure to reduce the risk of T2DM(OR = 0.666,95% CI = 0.457-0.970,P = 0.034).The wild type AA carrier of LncRNA CDKN2B-AS1 Gene Single-nucleotide polymorphism RS10965215 may interact with central obesity and increase the risk of T2DM(OR = 1.890,95% CI = 1.088-3.282,P = 0.024).The wildtype GG carrier of LncRNA CDKN2B-AS1 gene Single-nucleotide polymorphism RS10738605 interacted with central obesity and increased the risk of T2DM(OR = 2.064,95% CI = 1.201-3.547,P = 0.009).5.Effects of LncRNA CDKN2B-AS1 single nucleotide polymorphisms rs10965215 and rs10738605 on left ventricular diastolic function in T2DMIn T2 DM patients,compared with the wild AA genotype group and the heterozygous AG genotype group,the ultrasonic parameters lat e’ value and GLS value of rs10965215 mutant genotype GG group increased,while E /e ’value decreased,with statistically significant differences(P < 0.05).In the T2 DM group,compared with the wild GG genotype group and the heterozygous GC genotype group,the ultrasonic parameters lat e’ value and GLS value of rs10738605 mutant genotype CC group increased,while the value of E /e’decreased,with statistically significant differences(P < 0.05).Conclusion:1.LncRNA CDKN2B-AS1 single nucleotide polymorphisms rs10965215 and rs10738605 were associated with the risk of T2 DM,and both rs10965215 and rs10738605 reduced the risk of T2 DM.2.Stratified analysis showed that LncRNA CDKN2B-AS1 single nucleotide polymorphism rs10965215 could reduce the risk of T2 DM in non-drinking population.Hierarchical analysis showed that LncRNA CDKN2B-AS1 single nucleotide polymorphism rs10738605 reduced the risk of T2 DM in people younger than 55 years old.3.There was no significant interaction between genotype rs10965215 and genotype rs10738605 of LncRNA CDKN2B-AS1 Single-nucleotide polymorphism.4.Interaction between genotype AG and non-alcohol exposure in the Single-nucleotide polymorphism gene of LncRNA CDKN2B-AS1 reduces the risk of T2 DM.The interaction between wild-type AA carrier of polymorphism locus rs10965215 and central obesity increases the risk of T2 DM.The interaction between wild-type GG carrier of polymorphism locus rs10738605 and central obesity increased the risk of T2 DM.5.The genotypes rs10965212 and rs10738605 in the case group,and the patients with rs10965212 mutant genotype GG and rs10738605 mutant genotype CC had less impaired left ventricular diastolic function and might have a protective effect on cardiac function. |
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