| Objective: This study aimed to explore the association between UCP3(Uncoupling protein 3)and GHR(Growth hormone receptor)polymorphisms and T2DM(type 2 diabetes mellitus)and related metabolic indicators,as well as explore the impact of UCP3 and GHR polymorphisms and PA / SB(physical activity / sedentary behavior)interaction on T2 DM,explore the risk factors of T2 DM,and provide a basis for the prevention and treatment of T2DMMethods: The subjects included in this study were all Guangxi Han people,929 in the T2 DM case group and 1044 in the control group.Physical activity and sedentary behavior data were collected through questionnaires.Blood samples of the subjects were collected to conduct metabolic index detection and DNA extraction.UCP3 rs7930460 and rs590336 and GHR rs6180 was genotyped using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF-MS).Plink software was used for Hardy-Weinberg genetic balance test.SPSS 24.0 binary classification Logistic regression was used to analyze the association between gene polymorphisms and T2 DM,and the interaction between gene polymorphism and PA/SB;SPSS 24.0 multiple linear regression was used to analyze the association between gene polymorphisms and metabolic indicators;SHEsis online platform was used to conduct linkage disequilibrium and haplotype analysis of the two SNPs of UCP3.Results:(1)Comparison of general conditions and biochemical indicators of the study subjects: The baseline study subjects included in this study were a total of 1973 cases,including 929 patients,with an average age of 60.9 ± 10.0 years,and 1044 healthy controls,with an average age of 60.0 ± 9.5 years old.The male and female proportions of the patient group were respectively 39.2% and 60.8%,and the male and female proportions of the control group were respectively 37.7%and 62.3%.There was no statistically significant difference in age,gender,drinking status,physical activity and sedentary behavior status,and activity intensity during work between the two groups(P > 0.05).The smoking rate and BMI of the patient group were higher than those of the control group,and the difference was statistically significant(P < 0.05).Regarding biochemical indicators,the levels of SBP,DBP,TC,TG,Hb A1 c,FBG,2h PG,HOMA-IR,and FINS in the patient group were significantly higher than those in the control group,and the HDL-C levels of the patient group were lower than that of the control group.The difference was statistically significant(P < 0.05).(2)The association between gene polymorphisms and T2DM: the rs7930460 and rs590336 of UCP3 and the rs6180 of GHR gene,the frequency distribution of the three SNPs are in accordance with Hardy-Weinberg genetic balance law(P >0.05).The distribution of alleles and genotypes at the three SNPs was not statistically different between the patient group and the control group(P > 0.05).In the general population,no alleles and genotypes at the three SNPs were found to be associated with the risk of T2DM(P > 0.05).(3)The interaction between gene polymorphisms and PA/SB: after subgroup analysis based on physical activity and sedentary behavior conditions,no correlation between UCP3 rs7930460 and rs590336 and T2 DM risk was found in any subgroup(P > 0.05),and there was no interaction between these two SNPs and physical activity and sedentary behavior(P > 0.05).For the rs6180 of GHR gene,the AA genotype of rs6180 was found to be associated with an increased risk of T2 DM in people with insufficient PA,people with SB ≥ 3h/d and people with insufficient PA and SB ≥ 3h/d(P < 0.05).Through interaction analysis,it was found that rs6180 polymorphism interacted with sedentary behavior.In addition,after combining physical activity with sedentary behavior,rs6180 polymorphism interacted with PA/SB(P < 0.05).(4)The relationship between gene polymorphisms and metabolic indicators:in the total population,for the rs7930460 of UCP3 gene,individuals with GG genotype had lower levels of Hb A1 c and 2h PG than those with AA or AG(P <0.05);In the total population,for the rs590336 of UCP3 gene,individuals with TT genotype had lower 2h PG levels and higher HDL-C than those with CC and TC level(P < 0.05).Subgroup analysis found that TT genotype was still associated with higher HDL-C in the subgroup with sufficient PA and SB < 3h/d(P < 0.05).For rs6180 of GHR,in the general population,no rs6180 polymorphism was found to be associated with any metabolic indicators(P >0.05).Subgroup analysis found that in the population with insufficient PA and SB≥ 3h/d,individuals with AA genotype had higher Hb A1 c,FBG,2h PG and lower HDL-C than those with CC or CA genotype(P < 0.05).(5)Haplotype and linkage disequilibrium analysis: Haplotype analysis of the two SNPs of UCP3 revealed that none of the three haplotypes were related to T2DM(P > 0.05).Conclusion:(1)In the general population,this study did not find the rs7930460 and rs590336 of the UCP3 gene and the rs6180 of the GHR gene to be associated with T2 DM,and found no interaction between UCP3 gene polymorphism and PA/SB.(2)In the subgroup analysis,it was found that the GHR rs6180 AA mutant genotype may be associated with the increased risk of T2 DM in people with insufficient PA,people with SB ≥ 3h / d and people with insufficient PA and SB≥ 3h / d.There was an interaction between GHR gene polymorphism and PA/SB.Long sedentary time alone or combined with insufficient physical activity can both affect the association between GHR gene polymorphism and T2 DM.(3)In the general population,the UCP3 rs7930460 GG mutant genotype may be related to the decrease of Hb A1 c and 2h PG;the UCP3 rs590336 TT mutant genotype may be related to the decrease of 2h PG and the increase of HDL-C.(4)GHR rs6180 polymorphism is not found associated with metabolic indicators in the general population;In people with insufficient PA and SB ≥ 3h /d,it was found that the GHR rs6180 AA mutant genotype may be associated with the increase of Hb A1 c,FBG,2h PG and the decrease of HDL-C. |
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