Association Of ALDH2 Gene Polymorphism With Nonalcoholic Fatty Liver And Coronary Heart Disease In Guangzhou Population

Purpose:With the development of social economy,the prevalence of non-alcoholic fatty liver disease and coronary heart disease in China is increasing year by year,which has a serious impact on people’s health and national medical burden.The main purpose of this study was to observe the distribution of single nucleotide polymorphism(Glu504Lys)in exon 12 of the ALDH2 gene in Guangzhou population and to see if it meets the Hardy-Weinberg equilibrium.Based on this,the association between ALDH2 gene polymorphisms and non-alcoholic fatty liver disease and coronary heart disease was explored.Method:The study population selected the Guangzhou population who were admitted to the Guangzhou First People’s Hospital from December 2015 to May 2017.There were no kinships among all the cases.There were 644 cases(male 354,female 290 cases).They were divided into 4 groups: control group(group A),non-alcoholic fatty liver group(group B),coronary heart disease group(group C),and non-alcoholic fatty liver complicated with coronary heart disease group(group D);In group A,there were 273cases(male156,female 117 cases)with a mean age of 62.0±9.1 years;98 casess in B group(male 52,female 46 cases),with a mean age of 60.2±11.3 years;193 cases in group C(male 102,female 91 cases),with a mean age of 69.4±12.2 years;group D,80 cases(male 44,female 36 cases),with a mean age of 67.2±10.4 years old.The diagnosis of non-alcoholic fatty liver disease was based on "Guidelines for the diagnosis and treatment of non-alcoholic fatty liver disease in China(2010 revision)",excluding liver cancer patients.Diagnosis of coronary heart disease was diagnosed bycoronary angiography results according to the 1979 WHO diagnostic criteria.Analysis of the three branches of the coronary artery and left main lesions,stenosis> 50% defined as coronary heart disease,including stable angina,unstable angina,non-ST elevation myocardial infarction,ST-elevation myocardial infarction,rule out acute myocardial Infarct acute phase,connective tissue disease,grade III or higher cardiac insufficiency,variant angina caused by coronary spasm,various cardiomyopathy(except coronary heart disease ischemic cardiomyopathy),uncontrolled high blood pressure(blood pressure ≥180/100mmhg).Those who were selected were all that expected severe hepatic and renal insufficiency,malignant tumors,pancreatitis,autoimmune diseases,long-term use of glucocorticoid drugs,acute infectious diseases,diabetic,severe smoking and drinking.The control group had neither non-alcoholic fatty liver nor coronary heart disease.We collected general patient data,including body mass index(BMI),age,gender,blood pressure,smoking history,drinking history,fatty liver,coronary heart disease and other medical history,and biochemical tests included TG(triglyceride),Cr(creatinine),FPG(fasting Blood glucose,TC(total cholesterol),LDL-C(low density lipoprotein cholesterol),HDL-C(high-density lipoprotein cholesterol),ALT(glutamic-pyruvic transaminase),AST(glutamic-oxaloacetic transaminase)TBIL(total bilirubin),DBIL(direct bilirubin)and so on.After venous blood was collected for genotyping,the genomic DNA of peripheral venous blood was firstly extracted using a related instrument and used as a template for PCR(polymerase chain reaction),and then used DNA microarray to analyze ALDH2 gene polymorphism.At last,we recorded individual genotypes.SPSS 16.0 software was used for statistical analysis.Qualitative data were analyzed by using the Chi-square test,while quantitative data were analyzed by using the variance test.Statistically significant differences were included in the regression equation for Logistic regression analysis.P<0.05 indicated that the difference was statistically significant.Result:(1)The polymorphism of the ALDH2 genotype Glu504 Lys in the Guangzhou population corresponds to the discipline distribution of Hardy Weinberg’s genetic equilibrium law.(2)There are three genotypes of the ALDH2 gene Glu504 Lys polymorphism in Guangzhou population.They are Glu504 Glu,Glu504Lys,and Lys504 Lys.The distribution of ALDH2 gene in the subjects: the percentages of the three genotype individuals are57.88%,37.36% and 4.76% in groud A,28.57%,59.18% and 12.24% in groud B,58.03%,37.31% and 4.66% in groud,77.50%,15.00% and 7.50% in groud D.There was a statistically significant difference in genotype frequency(χ2=50.572,P<0.001),and a statistically significant difference in allele frequency(χ2=19.638,P<0.001).Further using the χ2 segmentation method to compare the differences between the two genotypes.Among them,the differences between A-B,A-D,B-C,B-D,and C-D groups were statistically significant(χ2=23.306,P<0.001;χ2=14.266,P=0.001;χ2=23.866,P< 0.001;χ2= 43.700,P <0.001;χ2 = 13.337,P = 0.001);A-C group differences were not statistically significant(χ2 = 0.003,P = 0.999).(3)Body mass index,triglyceride,age,serum creatinine,and Lys mutations entered the regression equation.Body mass index,triglyceride,age,and serum creatinine were risk factors for coronary artery disease complicated by NAFLD(OR>1).Lys mutations The type was protective factor(OR<1);the ALDH2 gene polymorphism distribution correlated with the number of risk factors exposed in patients with non-alcoholic fatty liver associated with coronary heart disease,there was a statistically significant difference(χ2=7.190,P=0.027).Chi-squared segmentation further analysis showed that there was a significant difference in gene frequency between non-alcoholic fatty liver associated with coronary heart disease patients with 1 risk factor and 2 risk factors(χ2=4.844,P=0.028);and there was a significant difference in gene frequency between non-alcoholic fatty liver associated with coronary heart disease patients with 2 risk factor and 3 risk factors(χ2=6.860,P=0.009);however,there was no statistically significant difference in the distribution of Glu504 Lys between patients with 2 risk factors and 3 risk factors(χ2=0.568,P=0.451).The distribution of genotypes in all risk factors met Hardy-Weinburg’s law of genetic equilibrium(P>0.05).Conclusion:1.ALDH2 gene single nucleotide polymorphism(Glu504Lys)exists in Guangzhou population.2.ALDH2 gene Glu504 Lys polymorphism is associated with nonalcoholic fatty liver.3.ALDH2 gene Glu504 Lys polymorphism is associated with non-alcoholic fatty liver associated with coronary heart disease,and Lys mutant is a protective factor for non-alcoholic fatty liver with coronary heart disease.4.ALDH2 Gene Glu504 Lys Polymorphism correlates with coronary heart disease complicated with NAFLD,and Lys mutation is a protective factor for coronary heart disease complicated with NAFLD.5.This study suggests that age,serum creatinine,triglyceride,and BMI are risk factors forcoronary heart disease complicated by NAFLD,while Lys mutation is a protective factor for coronary heart disease complicated by NAFLD.6.The polymorphism distribution of ALDH2 gene was associated with the number of risk factors for exposure in patients with coronary heart disease complicated by nonalcoholic fatty liver.