Association Between GCKR Rs780094 Gene Polymorphism In Patients With Premature Coronary Heart Disease Complicated With Hyperuricemia And Related Factors And Prognosis

With the development of the economy and the improvement of people’s lives,the prevalence of hyperuricermia is gradually increasing.In addition to traditional risk factors,premature coronary heart disease may have genetic factors,and the prevalence of hyperuricemia is higher.Evidence-based medical evidence suggests that hyperuricemia is associated with cardiovascular disease.Studies have shown that environment,metabolism,genetic inheritance and other factors are closely related to its occurrence and development.Single nucleotide polymorphism(SNP),mainly refers to DNA sequence polymorphism caused by single nucleotide variation at the genomic level,which was one of the important reasons for different susceptibility to disease among different individuals.In the past few decades,genome-wide association studies(GWAS)and other related studies have identified a number of uric acid-related genes((PDZKI,GCKR,LRP2,SLC2A9,ABCG2,LRRC16A,SLC17A1,SLC117A3,SLC22A11,SLC22A12,and SF1).Current research confirms that these genes can affect uric acid levels by affecting the re-absorption and secretion of uric acid in the renal tubules.However,the relationship between the uric acid susceptibility gene polymorphisms identified by GWAS and the association and prognosis of coronary heart disease remains unknown.This article aims to investigate the association between GCKR rs780094 gene polymorphism in patients with premature coronary heart disease complicated with hyperuricemia and related factors and prognosis,whicth provided a reference for the prevention and treatment of premature coronary heart disease.Subjects and methodsAll subjects were selected at Southern Theater General Hospital from January 2017 to January 2018.There were 148 patients with premature coronary heart disease who did not have hyperuricemia,and 92 patients with premature coronary heart disease complicated with hyperuricemia,aged between 22-55.Basic personal data such as height,weight,course of illness,dietary habits,smoking and alcoholism were recorded.All the blood samples came from Southern Theater General Hospital.The study was approved by the ethics committee,and all subjects gave their informed consent to the study.The whole process of blood sample collection is carried out in accordance with the requirements of standardization.The clinical biochemical indicators of all blood samples are tested by fully automatic biochemical analyzers.The data of blood glucose,blood lipid,uric acid,blood pressure and creatinine were recorded.The DNA extraction kit was used to extract the genomic DNA samples of the subjects and the genotypes of the two groups of subjects at the rs780094 site of the GCKR gene were detected by MassArray Flight Mass Spectrometry Biochip Technology.All subjects were included in the survival study survey,using telephone or outpatient follow-up.The longest follow-up time is 21 months,and the shortest follow-up time is 6 months,with an average of 12 months.The survey included the Pittsburgh sleep quality index and post-discharge diet,alcohol consumption,smoking status,working status,uric acid level,exercise status,and disease progression statusStatistical analysis was performed on the data using software SPSS 20.0 Kolmogorov-Smirnov method was used to test the normality of the measurement data.The normal distribution measurement data was expressed by mean±standard deviation.The comparison between groups was performed by T test.The skewed distribution data directly performed non-parametric test.The count data is expressed as a rate,and the comparison between groups is represented by a chi-square test.The Kaplan-Meier method was used to describe the patient survival curve.Log-rank test was used to assess the univariate analysis between demographic characteristics,clinical features and univariate analysis of MACCE during follow-up period Statistically significant variables(P<0.05)from univariate analysis were included in the COX risk regression model,step by step regression analysis.All analyses were performed on both sides,with P<0.05 indicating statistical significance.Results1.The average levels of triglycerides in two groups were 1.70±1.46mmol/1 and2.24±1.92 mmol/1 respectively,which were significantly higher in the premature coronary heart disease complicated with hyperuriccemia group than the non-hyperuricemia group(P=0.022).There were no statistical differences in the distribution of baseline,such as hypertension prevalence,blood pressure,diabetes prevalence,fasting blood glucose level,and body mass index between the two roups(P>0.05).There were no significant differences in the application history of aspirin,statins,beta blockers,and ACEI,diuretic between the two groups.2.Univariate logistic regression analysis showed that the GCKR rs780094 genotype was not associated with the prevalence of hyperuricemia in patients with coronary heart disease;this correlation was still not significant after adjusting for BMI,smoking,blood glucose,and blood lipids(P<0.05).3.The COX regression model showed that the rs780094 gene polymorphism had no significant effect on the prognosis of patients with premature coronary heart disease who did not have hyperuricemia(P>0.05).4.Univariate survival analysis found that sleep quality were closely related to the prognosis of patients with premature coronary heart disease(P=0.006),and FPG level was closely related to the prognosis of patients with premature coronary heart disease without hyperuricemia(P=0.015).5.Multivariate analysis showed that sleep quality were the risk factors affecting the progression and prognosis of patients with premature coronary heart disease(P=0.001).With sleep PSQI(0-5 points)as reference,patients with sleep PSQI(6-10 points)and PSQI(11-15 points)significantly increased the risk of cardiovascular events(HR=2.178,95%CI:1.302-3.646,P=0.003)and(HR=2.759,95%CI:1.253-6.232,P=0.012).Fasting blood glucose levels were closely related to the prognosis of patients with premature coronary heart disease who did not have hyperuricemia(P=0.015).Compared with patients with fasting blood glucose≤5.9mmol/1,patients with fasting blood glucose>5.9mmol/I had a higher risk of developing adverse cardiovascular and cerebrovascular events after discharge(HR=0.418,95%CI:0.226-0.774,P=0.006).Conclusion:1.There was no significant association between GCKR rs780094 gene polymorphism and susceptibility to premature coronary heart disease complicated with hyperuricemia.2.GCKR rs780094 gene polymorphism has no significant effect on the prognosis of patients with premature coronary heart disease with or without hyperuricemia during follow-up..3.Decreased sleep quality was a risk factor for cardiovascular events in patients with premature coronary heart disease.