Association Between Polymorphism Of KCNQ1 Gene Rs151290,rs2237892 And Non-alcohoic Fatty Liver Disease With Coronary Artery Disease

Background Nonalcoholic fatty liver disease(NAFLD)is a common chronic liver disease worldwide.It is predicted that the number of people affected by NAFLD and its complications will continue to rise in the next few years,which increasing the global health burden.Nonalcoholic fatty liver disease is an independent risk factor for coronary heart disease(CAD).These two diseases often exist in one patient.Metabolic syndrome is the connection between NAFLD and CAD.Both NAFLD and CAD are multi-gene hereditary diseases,which affected by genetics and environment.In 1996,Wang discovered the KCNQ1 gene for the first time in patients with LQTS1.KCNQ1 belongs to the KCNQ family of voltage-gated potassium channels and is a member of a large class of genes,which encodes a voltage-gated potassium channel protein and expresses in many tissues.Studies have reported that KCNQ1 is associated with cardiovascular disease,but the conclusions are currently inconsistent.The other studies showing that KCNQ1 is related to the progress of NAFLD.However,the genetic data of NAFLD and CAD related to KCNQ1 are still incomplete,and the correlation between KCNQ1 gene polymorphisms and NAFLD combined with CAD diseases is lack.Therefore,this study was conducted among some people in the Qingdao area.Objective The present study is to investigate the correlation between KCNQ1 gene rs2237892,rs151290 polymorphism and NAFLD,CAD and NAFLD combined with CAD in some people in Qingdao.Methods 603 patients were enrolled in total in this study.Divided into four groups,namely NAFLD patients,CAD patients,NAFLD combined CAD patients,and healthy people were selected from the Qingdao Municipal Hospital.140 NAFLD patients(98 M/ 42 F),194 CAD patients(123 M/71 F);92 NAFLD combined with CAD patients(64 M/28 F),177 healthy controls(107 M/70 F).General clinical data and relevant biochemical indicators of subjects were collected.The biochemical indicators include Total Cholesterol,triglyceride,high-density lipoprotein,Low-density lipoprotein,alanine aminotransferase,aspartate aminotransferase,γ-glutamyl transferase,alkaline phosphatase,total bilirubin,and fasting blood glucose.The genotypes of rs1512290 and rs2237892 locus of KCNQ1 gene was determined by PCR and flight mass spectrometry(MALDI-TOF MS).The Hardy—Weinberg was used to evaluate the representative of the group.SPSS22.0 was used for statistical analysis.Tests for normal distribution of measurement data,chi square tests,t tests and Wilcoxon rank sum tests were used to compare the data of genotypes and clinical features.Results(1)The sequencing found that the KCNQ1 gene rs2237892 has three genotypes of AA,AT and TT.rs151290 has three genotypes of AA,AC and CC.After testing,the genotypes of rs22337892 and rs151290 of KCNQ1 gene conform to the Hardy-Weinberg equilibrium law and are representative of the population.(2)There is no significant difference of genotypes in KCNQ1 rs2237892 between the CAD group and control group,NAFLD group and CAD group,NAFLD group and control group,NAFLD group and NAFLD&CAD group,NAFLD&CAD group and control group,CAD group and NAFLD&CAD group(P=0.741,P=0.189,P=0.480,P=0.412,P=0.110,P=0.065).The distribution of the A and T alleles is also not statistically significant(P=0.463,P=0.080,P=0.293,P=0.962,P=0.383,P=0.140)There is no significant difference of genotypes in KCNQ1 rs151290 between the NAFLD group and CAD group,NAFLD group and control group,NAFLD group and NAFLD&CAD group,CAD group and control group,CAD group and NAFLD&CAD group,NAFLD&CAD group and control group(P=0.685,P=0.270,P=0.933,P=0.189,P=0.672,P=0.564).The distribution of the A and C alleles is also not statistically significant(P=0.446,P=0.285,P=0.876,P=0.725,P=0.616,P=0.437)。(3)In the CAD group of KCNQ1 rs2237892 T allele carriers have higher ALT and TG than those who don’t carry T alleles(P=0.035,P=0.015).In NAFLD&CAD group,T allele carriers have higher TG than those who don’t carry T alleles(P=0.023).(4)In the CAD group of KCNQ1 rs151290 C allele carriers have higher ALP than those who don’t carry C alleles(P=0.039).Conclusion The KCNQ1 gene rs2237892,rs151290 polymorphism has no significant correlation with the risk of NAFLD,CAD,and NAFLD combined CAD in some populations in Qingdao area.Parts of the serum lipids indicators are significant higher in the rs2237892 mutation carriers than in the wildtype carriers in CAD and NAFLD combined CAD patients.