Association Of Transmembrane 6 Superfamily 2 Gene Polymorphisms With The Risk Of Coronary Artery Disease In Patients With Nonalcoholic Fatty Liver Disease In A Chinese Han Population

Background:Both nonalcoholic fatty liver disease(NAFLD)and coronary artery disease(CAD)are associated with significant morbidity in the worldwide.Meanwhile,they are also common diseases in China.The abnormal serum lipid profiles play an important role in the onset and progression of these two diseases.Besides,NAFLD is considered as the manifestation of metabolic syndrome in the liver.The mainly characteristics of dyslipidemia of NAFLD are high concentration of the low-density lipoprotein choles-terol(LDL-C)and triglyceride(TG)with the low concentration of high-density lipo-protein cholesterol(HDL-C),which can also promote the progress of CAD.The main bridge between the two diseases is the disorder of lipid metabolism,which can promote the progress of each other form a vicious cycle.Therefore,we expect to find potential therapeutic targets to break the vicious cycle by exploring the possible mechanism that affects the lipid metabolism between the two diseases.It maybe provides a new direc-tion for the real individualized treatment in the future.TM6SF2 rs58542926,as one of the new targets for regulating lipid metabolism,has attracted much attention in recent years.The existing animal model and in vitro cell culture model have confirmed that TM6SF2 rs58542926 can reduce serum lipid profiles to a certain extent.At present,the conclusion about the relationship between TM6 SF2 rs58542926 and cardiovascular disease(CVD)is basically the same.That is,TM6SF2 rs58542926 plays a protective role in the progression of CAD.However,some disputes about whether it can cause li-pid accumulation in the liver and about specific mechanism of it are still unsettled.That is,whether it is a risk factor for NAFLD is controversial.Objectives:The purpose of this study was to furtherly clarify the relationship between TM6SF2 rs58542926 and NAFLD as well as that between M6SF2 rs58542926 and CAD.In addition,we firstly explored the relationship among TM6SF2 rs58542926,CAD and NAFLD combined with CAD in a Chinese Han Population.Materials and Methods:From January 1,2017 to December 31,2017,we collected totally 578 patients re-spectively with CAD,NAFLD,NAFLD combined with CAD and healthy controls.The188 patients of them were in group CAD(120 M/68 F),the 150 patients of them were in group NAFLD(95 M/55F),the 118 patients of them were in group NAFLD with CAD(80M/38F),and the 122 patients of them were in the control group(68M/54F).The collected information included the clinical basic information of the patient,the re-sults of laboratory examination related to blood lipids and the genotype of TM6SF2rs58542926.The?~2 test analysis were used for count data and the comparison between two groups.The measurement data were analyzed by t test.The relative risk degree of rs58542926 polymorphisms and NAFLD was compared with the ratio Ratio(OR)and its 95%confidence interval(CI)which were calculated by using the logistic regression analysis model.Result:The results of comparison of clinical data are as follows.Compared with the group control,the indexes of age,BMI,SBP,AST,GLU and TG were higher and the indexes of TC,HDL and LDL were lower in the group NAFLD combined CAD(P<0.05).Compared with group CAD,the index of age was lower and the indexes of DBP was higher in the group NAFLD combined CAD(P<0.05).Compared with the group control,the indexes of age,SBP,BMI,AST,GGT and GLU were higher and the indexes of DBP,TC,HDL and LDL were lower in the group CAD(P<0.05).Compared with the group control,the indexes of BMI,SBP,DBP,GGT,TG and TC were higher and indexes of the age was lower in the group NAFLD(P<0.05).The results of comparison of the dis-tribution of genotypes and alleles are as follows.The distribution difference of the gen-otypes between the group control and the group NAFLD as well as that between the group control and the group CAD had a statistically significant(P<0.05).The distribu-tion difference of alleles between the group CAD and group control had a statistically significant(P<0.05).Logistic regression analysis showed that TM6SF2 rs58542926significantly decreased the risk of CAD(OR=0.231,95%CI,0.060~0.889,P=0.033).And after adjusting for confounding factors of age,gender and BMI,the result of lo-gistic regression analysis was still statistically significant(OR=0.207,95%CI,0.047~0.907,P=0.037).The results of comparison of clinical indexes between the different genotypes of TM6SF2 in the different groups are respectively as follows.Among all the participants,the differences in age,DBP,ALP,TC and LDL between the different gen-otypes of TM6SF2 were statistically significant(P<0.05).In group NAFLD combined CAD the difference in DBP between the different genotypes of TM6SF2 was statisti-cally significant(P<0.05).In the group NAFLD,the differences in GGT,ALP,TC and LDL between the different genotypes of TM6SF2 were statistically significant(P<0.05)We found no significant difference in various clinical indexes in the group CAD and the group control(P>0.05).Conclusion:There was no significant correlation between the TM6SF2 rs58542926 and the risk of developing NAFLD in the Han population in the Shandong region.However,TM6SF2 rs58542926 can significantly reduce the risk of developing CAD in the Han population in the Shandong region.In comparison with the three groups of NAFLD combined with CAD,CAD and control groups,we found no significant correlation be-tween the carrying of TM6SF2 rs58542926 in the CAD population or in the healthy population and the morbidity of NAFLD combined with CAD.However,the follow-up study still needed to continue to explore it.