Association Between Polymophism Of PCSK9 Gene E670G And Non-alcoholic Fatty Liver Disease With Coronary Heart Disease

BackgroundNon-alcoholic fatty liver disease(NAFLD)is a metabolic stress liver disease closely related to insulin resistance and genetic susceptibility.It has now replaced hepatitis B as the world's largest chronic liver disease.NAFLD contains a series of pathological changes that include non-alcoholic steatohepatitis(NASH),liver fibrosis,cirrhosis,and even hepatocellular carcinoma(HCC).The prevalence of NAFLD in the world is about 25%.In recent years,the prevalence of NAFLD in China has increased significantly and is in a younger age.NAFLD is one of the enormous disease burdens facing the world that endangers human health and social development.The occurrence and development of NAFLD is the result of a combination of factors.NAFLD is closely related to the pathogenesis of extrahepatic diseases,especially coronary heart disease,and coronary heart disease is also the main cause of death in patients with NAFLD.The PCSK9 gene is the third gene found in 2003 that is associated with the pathogenesis of autosomal dominant hypercholesterolemia and is also considered to be a risk factor for coronary heart disease and atherosclerosis.The PCSK9 gene promotes the degradation of mature LDLR by encoding the proprotein convertase subtilisin 9,which interferes with the uptake of LDL-C and affects the level of cholesterol.The PCSK9 E670 G locus is a widely studied genetic locus and is thought to affect blood lipid levels and the severity of coronary atherosclerosis.A large number of studies have shown that NAFLD and CAD have common risk factors,often in the same individual,but there is no study on the association between PCSK9 E670 G gene polymorphism and NAFLD combined with coronary heart disease.ObjectiveThis study is aim to investigate the correlation between PCSK9 gene E670 G polymorphism and NAFLD,CAD and NAFLD combined with CAD in the Han population of Qingdao,China.And to explore the possible Mechanism and prevention guidance for NAFLD and CAD.MethodsThis study enrolled 144 NAFLD patients,208 patients with CAD,95 patients with NAFLD combined CAD,and 176 healthy individuals in Qingdao Municipal Hospital.The general clinical data and blood samples were tested for biochemical correlation,and the genotype of PCSK9 E670 G locus was detected by polymerase chain reaction(PCR)and flight mass spectrometry(MALDL-TOF-MS).Population representativeness was tested by Hardy-Weinbeurg's law of genetic balance.Statistical software SPSS 25.0 was used to analyze the clinical data and genotypes of the subjects by statistical methods.Results(1)There were statistically significant differences in age,gender,BMI,fasting blood glucose,total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein,ALT,AST,GGT,and ALP between the four groups(P< 0.05).(2)There was no obvious variation of genotypes between the CAD and control group,NAFLD and control group,NFALD combined with CAD group and control group,NAFLD group and combined group,CAD and combined group(P=0.781,P=0.892,P=0.811,P=0.681,P=0.725),and the distribution of A and G alleles was not statistically different(P=0.499,P=0.513,P=0.545,P=0.249,P=0.460).(3)Carrying the PCSK9 gene E670 G mutation did not increase the risk of NAFLD,CAD and NAFLD combined with CAD.(4)Among all candidates,PCSK9 gene E670 G AG+GG carriers show a significantly higher serum LDL and TC levels compared with AA carriers(P <0.05).ConclusionThe PCSK9 gene E670 G polymorphism shows no relation to the risk of NAFLD,CAD,NAFLD combined CAD in China.But the level of total cholesterol and low density lipoprotein are associated with the polymorphism of PCSK9 E670 G.