| Objective: Uncoupling protein 1(UCP1)plays an important role in energy metabolism and mitochondrial reactive oxygen species,and is involved in the pathogenesis of type 2 diabetes.This study was designed to screen for factors affecting type 2 diabetes,detect UCP1 gene polymorphism,explore the association between UCP1 gene polymorphism and type 2 diabetes,and further explore the interaction between UCP1 gene-environment factors for type 2 diabetes.Providing scientific basis for the pathogenesis and prevention of type 2 diabetes.Methods: Taking the physical examination population of the First Affiliated Hospital of Guangxi Medical University as the research objects,a case-control study using 1:1 matching of gender and age(± 5 years old)was conducted.A total of 900 pairs of case-controls were included.Questionnaire survey,physical examination and biochemical indicators were performed on 900 pairs of casecontrols,and blood samples were extracted.Three SNPs on the UCP1 gene(rs3811790,rs3811791,rs1472268)were genotyped by MassARRAY detection technique.The database was established by Epidata 3.1 software.The Hardy-Weinberg genetic equilibrium test,the allele frequency and genotype frequency distribution of each SNP locus were analyzed by Plink 1.07 software.The linkage disequilibrium and haplotype analysis were performed using SHEsis online platform.The GMDR 0.9 software was used to analyze the gene-gene and geneenvironment interactions of each SNP locus in UCP1 gene by the generalized multifactor dimensionality reduction method.The rest of the statistical analysis was performed by SPSS 19.0 software.Results:(1)The final analysis of this study included 900 pairs of casecontrols.The gender distribution of the case group was consistent with that of the control group,including 358 males(39.78%)and 542 females(60.22%);the age of the case group was(64.67±10.02)years old.The age of the control group was(64.58±9.73)years old.There was no significant difference in age and gender distribution between the case group and the control group(both P>0.05).Multivariate analysis showed that risk factors for type 2 diabetes may be: regular smoking(OR=1.697,95%CI=1.045-2.755,P=0.033),overweight(OR=1.378,95% CI=1.072-1.770,P=0.012),obesity(OR=1.994,95%CI=1.382-2.878,P<0.001),high systolic blood pressure(OR=1.121,95%CI=1.040-1.207,P=0.003)and high triglycerides(OR=1.040,95% CI=1.022-1.058,P<0.001);protective factors for type 2 diabetes may be occasional drinking(OR=0.621,95% CI=0.452-0.852,P=0.003).(2)The rs3811790,rs3811791,and rs1472268 loci in the control group were consistent with Hardy-Weinberg’s genetic equilibrium(P>0.05).There were no significant differences in the distribution of the three loci allele and genotype frequencies in the UCP1 gene between the case group and the control group(P>0.05).After adjusting for smoking,alcohol consumption,and BMI,it was found that in the co-dominant model of rs3811791 locus,individuals with CT genotypes were found to have a reduced risk of type 2 diabetes compared with individuals with TT genotypes(OR=0.762,95%CI=0.593-0.980,P=0.034).No significant association with type 2 diabetes was found in the co-dominant,dominant,and recessive models of rs3811790 and rs1472268.(3)The haplotype analysis was performed on three sites of UCP1 gene.The distribution of the five haplotypes in the case group and the control group was not found to be statistically significant(P>0.05).(4)The results of generalized multifactor dimensionality reduction of geneenvironmental factors showed that rs3811790 interacted with age(P =0.001).(5)In the study population,adjusted for smoking,drinking,and BMI,we found that individuals carries CC genotype compared with TT genotype individuals of rs3811791 in co-dominant model,whose TG level was higher(P=0.011);the individuals carrying CC genotype in the recessive model of rs3811791 had higher TG levels than individuals carrying(CT+TT)genotypes(P=0.009).No association was found between rs3811790 and rs1472268 polymorphisms and metabolism of physiological and biochemical indicators.Conclusions:(1)Regular smoking,overweight and obesity,high systolic blood pressure,and high triglycerides may be risk factors for type 2 diabetes.Occasional drinking may be a protective factor for type 2 diabetes.(2)In the study population,individuals with CT genotypes at the rs3811791 locus of the UCP1 gene had a reduced risk of developing type 2 diabetes compared with individuals carrying the TT genotype.(3)The interaction of rs3811790,rs3811791,rs1472268 locus of UCP1 gene with environmental factors were found that rs3811790 may interact with age to increase the risk of type 2 diabetes.(4)In the study population,the CC genotype of rs3811791 at the UCP1 gene may be associated with elevated levels of triglycerides. |
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