| Objective:Type 2 diabetes mellitus（T2DM）is one of the three most common chronic noncommunicable diseases in the world and is characterized by insulin resistance and relative insufficiency of insulin secretion.At present,studies have shown that adiponectin（APN）plays a major role in glucose metabolism and insulin resistance,and is closely related to metabolic syndrome and T2DM.This study was conducted in Chinese Han population to analyze the correlation between the genetic variations in APN gene 3’untranslated region（3’UTR）and the T2DM through a case-control study,so as to provide genetic evidence for the disease risk factors of T2DM.Methods:Firstly,the adiponectin gene 3’UTR were sequenced in 50 NDM subjects.Eight SNPs of APN gene（rs56354395,rs6773957,rs1063537,rs2082940,rs1063538,rs4686804,rs1063539 and rs17846865）were selected according to sequencing results.Then,730 T2DM patients from the Department of Endocrinology,Affiliated Hospital of Yunnan University from September 2018 to April 2020 were randomly enrolled as the case group and 612 non-diabetic mellitus（NDM）subjects who underwent physical examination during the same period were randomly enrolled as the control group.The eight SNPs were genotyped by Taq Man probe fluorescence quantitative PCR.The two independent sample t-test and rank-sum test of completely random design data of two samples were used to analyze the differences of age and metabolic indexes between the two groups.Chi-square（x~2）test was used to analyze gender differences between the two groups.In the T2DM and NDM groups,the Hardy-Weinberg equilibrium（HWE）,alleles and genotypes frequencies,linkage disequilibrium（LD）and haplotypes were constructed for 8 SNPs loci by SHEsis online software.The analysis for model of inheritance was performed using SNPStats.The correlations between SNPs genotypes and glucose and lipid metabolic parameters in the two groups were analyzed by One-way analysis of variance（ANOVA）and rank-sum test of randomly designed multiple samples.Results:（1）There were no significant differences in age and gender between T2DM group and NDM group（P>0.05）.The differences in the levels of glucose and lipid metabolic parameters were statistical significance between the two groups（P<0.01）.The levels of TC,TG,LDL-C,FPG and Hb A1c in T2DM group were higher than those in NDM group,while HDL-C was lower than that in NDM group.（2）In this study,the adiponectin gene 3’UTR were sequenced in 50 NDM subjects.According to the sequencing results,there were 8 SNPs（rs56354395,rs6773957,rs1063537,rs2082940,rs1063538,rs4686804,rs1063539 and rs17846865）in this region.（3）HWE equilibrium analysis showed that rs56354395,rs6773957,rs1063537,rs2082940,rs1063538,rs4686804,rs1063539 and rs17846865 in NDM group were in accordance with HWE equilibrium（P>0.05）,and were representative of the population.（4）The differences of alleles and genotypes frequency distribution between rs56354395,rs6773957,rs1063537,rs2082940,rs1063538,rs4686804,rs1063539 and rs17846865in APN gene 3’UTR in the two groups were not statistically significant（P>0.05）.（5）The results of linkage disequilibrium showed that there were strong linkage relationships among SNPs rs56354395,rs6773957,rs1063538,rs4686804 and SNPs rs1063537,rs2082940,rs1063539.（6）Haplotype analysis showed that the rs56354395-rs6773957-rs1063538-rs4686804haplotype and rs1063537-rs2082940-rs1063539 haplotype had no significant differences in the frequency distribution between T2DM group and NDM group（P>0.05）.（7）Inheritance models analysis showed that the differences of the frequency distribution between the 8 SNPs in APN gene 3’UTR in the two groups were not statistically significant（P>0.05）.（8）Correlation analysis between genotype and metabolic index showed that in NDM group,the FPG of rs17846865T/T genotype was（4.84±0.56）mmol/L,Hb A1c was（5.10±0.39）%,and the FPG of rs17846865C/C+C/T genotype was（5.03±0.51）mmol/L,Hb A1c was（5.21±0.35）%.Compared with C/C+C/T genotype individuals,T/T genotype individuals had lower FPG（P<0.01）and Hb A1c（P=0.01）.The LDL-C of rs17846865T/T genotype was（2.23±0.71）mmol/L,and the LDL-C of rs17846865C/C+C/T genotype was（2.06±0.55）mmol/L.Compared with C/C+C/T genotype individuals,T/T genotype individuals had higher LDL-C（P=0.01）.There were no significant differences in glucose and lipid metabolic parameters among different genotypes of 3’UTR rs56354395,rs6773957,rs1063537,rs2082940,rs1063538,rs4686804 and rs1063539 in NDM group（P>0.05）.In T2DM group,there were no significant differences in glucose and lipid metabolic parameters among different genotypes of 3’UTR rs56354395,rs6773957,rs1063537,rs2082940,rs1063538,rs4686804,rs1063539 and rs17846865（P>0.05）.Conclusion:The 3’UTR genetic variations in APN gene were not associated with T2DM in Chinese Han population,but rs17846865 could be associated with the glucose and lipid metabolism in Chinese Han population. |
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