Association Of Nonalcoholic Fatty Liver Disease And Coronary Atherosclerotic Heart Disease With GCKR Polymorphism

Purpose: Accumulated studies have evaluated the effects of glucose kinase regulatory protein(GCKR)gene polymorphisms on the risk of nonalcoholic fatty liver disease(NAFLD)and coronary atherosclerotic heart disease(CAD),but the association of GCKR polymorphisms with the risk of NAFLD and CAD were remaining unclear in Chinese Han population.The aim of this study was to investigate the association between GCKR gene polymorphisms(rs780094 and rs1260326)with the risk of NAFLD and CAD in Chinese Northern Han population.Methods:(1)There are four groups of participants in this study,including healthy controls(n=152),NAFLD patients without CAD(n=142),CAD patients without NAFLD(n=154)and NAFLD patients with CAD(NAFLD+CAD,n=82).Fasting blood samples of all participants were collected for DNA test and biochemistry test.(2)The study collected general clinical characteristics and biochemical indicators,including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),fasting plasma glucose(FPG),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bilirubin(BIL),alkaline phosphatase(ALP)and Gama-glutamyl transferase(GGT).(3)GCKR rs780094 and rs1260326 gene polymorphism was using polymerase chain reaction(PCR)detection.Hardy Weinberg’s law of genetic balance test is used to test population representativeness.(4)Statistical analyses were conducted using SPSS 22.0 statistical software through the chi-square test,the logistic regression analysis and other statistical methods to explore the correlation of GCKR gene polymorphism and NAFLD,CAD,NAFLD+CAD susceptibility and the independent risk factor of NAFLD,NAFLD+CAD.P<0.05 was considered as statistical differences.Results:(1)There were no significant differences in age,gender,AST,BIL(P>0.05),while there were statistically significant differences in BMI,FPG,TC,TG,HDL-C,LDL-C,ALT,GGT,ALP between the four groups(P<0.05).(2)GCKR gene rs780094,rs1260326 CC and CT,TT genotype distribution had no significant statistical difference among the control group,NAFLD,CAD and NFALD+CAD group(P>0.05).GCKR gene allele distribution(C vs.T),dominant genetic model(CT+TT vs.CC)and recessive models(TT vs.CT+CC)also had no statistical difference(P>0.05).(3)In all the candidates,it was obvious that compared with the GCKR gene rs780094,rs1260326 CC carriers,CT/TT carriers have lower FPG levels(P<0.05),CT carriers have lower levels of TG(P<0.05).In controls,compared with the GCKR gene s780094,rs1260326 CC carriers,CT/TT carriers have lower levels of BMI and TG(P<0.05).In NAFLD+CAD,compared with the GCKR gene s780094 CC carriers,CT/TT carriers have lower levels of FPG(P<0.05).(4)Logistic regression analysis showed that compared with healthy controls,NAFLD was associated with higher BMI,TC(P<0.05);Compared with NAFLD group,NAFLD+CAD was associated with lower BMI,HDL-C and higher FPG(P<0.05).There was no significant correlation between GCKR rs780094,rs1260326 T allele and NAFLD,NAFLD+CAD(P>0.05).Conclusions:(1)GCKR rs780094 and rs1260326 gene polymorphism was not associated with the susceptibility of NAFLD,CAD and NAFLD+CAD in Qingdao population.(2)GCKR rs1260326 TT/CT genotype carriers were associated with the lower levels of BMI,FPG and TG.(3)Higher BMI and TC were associated with the risk of NAFLD;lower BMI,HDL-C and raised FPG were associated with the risk of NAFLD+CAD.GCKR rs780094,rs1260326 T allele and NAFLD,NAFLD+CAD susceptibility had no obvious correlation.