Association Between GCKR Polymorphisms And Metabolic Syndrome

ObjectivesTo explore the relationship between GCKR gene SNPs(Single Nucleotide Polymorphisms)and metabolic syndrome susceptibility in the Han population in northern China,to clarify the mechanism of GCKR SNPs-environment interaction in the development of metabolic syndrome,and to provide a theoretical basis for disease prevention and treatment.MethodsThis study applied the case-control study design.A total of 3754 subjects were included,including 1810 cases in the case group and 1944 cases in the control group.The age and gender of the two groups were matched.Online website Genome Variation Server and the function prediction website SNPinfo was used to select the SNPs of the GCKR gene.Finally,the four SNPs were selected:rs1260326,rs8179206,rs780094,and rs2293571.The genotyping of 4 SNPs on the GCKR gene was detected by high-energy MALDI-TOF-MS technology.Hardy-Weinberg equilibrium was tested by goodness-of-fitχ~2 test;the optimal genetic model of SNPs was selected by online analysis program SNPStats;the relationship between genotype and metabolic syndrome under each genetic model was determined by Logistic regression,and the efficiency of the optimal genetic model was analyzed by Quanto software;Combined with the selected environmental factors,the interaction between GCKR SNPs and environmental factors on the occurrence of diseases was determined by Logistic regression model.Results1.The general characteristics of the subjects:A total of 3754 subjects were included,including 1810 cases in the case group and 1944 cases in the control group.The case group is 49.00(43.00-57.00)years old,and the control group is 49.00(43.00-56.00)years old.There were 900 males(49.72%)in the case group,994 males(51.13%)in the control group.There was no significant difference in age and gender between the two groups(P>0.05);the difference in location,education,and occupation between the two groups was statistically significant(P<0.05).2.Hardy-Weinberg equilibrium test:The results showed that,except for rs780094 site that did not meet the in the control group(P<0.001),the remaining three sites(rs1260326,rs8179206,and rs2293571)met Hardy-Weinberg equilibrium(P>0.05)in the case group and the control group.3.Association analysis of GCKR gene polymorphism and metabolic syndrome:After adjusting for age,gender,location,education and occupation,under the optimal genetic model(recessive model),rs780094 is associated with metabolic syndrome(OR=0.753,95%CI:0.633-0.895,P=0.001).The calculated power for this SNP was93.59%.The rs1260326、rs8179206和rs2293571 were not associated with Met S(P>0.003125).4.Haplotype analysis:There was a statistically significant difference in the frequency of haplotype CAGC between the case group and the control group(OR=0.88,95%CI:0.79-0.98,P=0.019).There were no statistically significant differences in the distribution of other haplotypes(P>0.05).5.Gene-environmental interaction:the interaction of rs1260326/rs8179206/rs780094/rs2293571-drinking/grains intake/salt intake/red meat intake was not statistically associated with Met S(P>0.05).Conclusion1.In the recessive model,there is a genetic association between the rs780094locus on the GCKR gene and the metabolic syndrome,and the GCKR gene may be a susceptible gene for the metabolic syndrome.2.The haplotype CAGC composed of rs1260326,rs780094,rs8179206 and rs2293571 can reduce the risk of metabolic syndrome.3.There is no interaction between rs1260326,rs780094,rs8179206,and rs2293571 and drinking,grains intake,salt intake,red meat intake.