Association Between PNPLA3 Rs738409 Polymorphism With Non-alcoholic Fatty Liver Disease With Coronary Heart Disease In A Chinese Han Population

Background: Nowadays,Non-alcoholic fatty liver disease(NAFLD)is considered as the most prevalent chronic liver disease,and has become an important public health problem in the world.NAFLD progress from simple fatty liver to non-alcoholic steatohepatitis(NASH),liver fibrosis,cirrhosis,and even decompensation or liver cancer(HCC).The incidence of coronary atherosclerotic heart disease(CAD)is increasing year by year and has become the leading risk factor for cardiovascular disease,which leading to the large morbidity and mortality in the world.Both NAFLD and CAD are complex chronic diseases caused by the interaction between heredity and environment factors.Multiple studies have shown that the common pathogenesis of NAFLD and CAD include abnormal lipid metabolism,insulin resistance and oxidative stress,etc.Genome-wide association study(GWAS)has proved that PNPLA3 gene polymorphism is closely related to the development and progression of NAFLD,among which rs738409 is the most widely studied gene locus,which can prevent triglyceride hydrolysis,therefore leading to the accumulation of triglyceride and affecting serum lipids levels.Dyslipidemia is recognized as one of the important factors of coronary heart disease,and it is usually that patients suffer from the CAD and NAFLD at the same time.It is controversial for the association of PNPLA3 rs738409 with the risk of CAD in the previous studies,and no related data was available in China.Objectives: To investigate the potential relationship between PNPLA3 rs738409 and the risk of NAFLD,the risk of CAD,and the risk of NAFLD&CAD in Chinese Han population.Methods: Totally 600 subjects were enrolled in this study which were recruited from Qingdao Municipal Hospital from July 2018 to December 2018.These subjects include 145 NAFLD patients(83 M/62 F),199 CAD patients(112 M/87 F),96 NAFLD with CAD patients(56 M/40 F)and 160 healthy controls(74 M/86 F).Blood samples were collected,and DNA was extracted.The genotype of rs738409 locus of PNPLA3 gene was determined by PCR.General clinical data and laboratory biochemical indicators were also collected.In order to assess the group representativeness of samples,the chi-square test was used to test whether the distribution of genotypes was in accordance with the Hardy-Weinberg(H-W)equilibrium.We used SPSS24.0 to analyze the data,and chi square test,t test,Wilcoxon rank sum test and Logsitic regression analysis were used to compare the differences of genotypes and clinical features.Results: There was a prominent difference in allele and genotype distributions between the control group and NAFLD group,control group and NAFLD&CAD group,CAD group and NAFLD group,and CAD group and NAFLD&CAD group(all P<0.05).No significant difference was found between NAFLD group and NAFLD&CAD group,as well as between the control group and CAD group.In the NAFLD group,we found that,the serum TC,LDL,ALT,AST and GGT levels were dramatically increased in CG+GG genotype carriers.In the NAFLD&CAD group,CG+GG genotype carriers had higher serum levels of GLU,GGT and ALP.NO significant difference was found in various clinical indexes in CAD group and control group(all P>0.05)Conclusions: In the Chinese Han Population,PNPLA3 rs738409 polymorphism significantly increases the risk of NAFLD.However,it may not be an independent risk factor for CAD,and PNPLA3 rs738409 could not increase the risk of CAD in NAFLD patients.