Association Between DPP4 Gene Rs1558957?rs17848915 And Rs7608798 Polymorphisms With NAFLD In Chinese Han Population

Background Non-alcoholic fatty liver disease(NAFLD)is a widely prevalent chronic liver disease,which is a manifestation of metabolic syndrome in the liver.However,the pathogenesis of NAFLD has not yet been clarified,and it is generally believed to be the result of a combination of genetic,metabolic,and environmental factors.Numerous studies have shown that a variety of pathological processes such as insulin resistance(IR),dyslipidemia and oxidative stress promote the progression of NAFLD.Dipeptidyl peptidase-4(DPP4)is a membrane-associated peptidase that is widely distributed in the body and has a high concentration in hepatocytes.DPP4 plays an important role in many cellular activities such as glucose metabolism,fat accumulation,immune regulation,signal transduction,inflammatory response,vascular function and apoptosis.Studies at home and abroad have shown that DPP4 is closely related to the progression of NAFLD,but there are few reports on the relationship between this gene polymorphism and the susceptibility to NAFLD.Objective To detect the polymorphisms of DPP4 gene rs1558957,rs17848915 and rs7608798 and serum DPP4 levels in Han population of Qingdao,and to explore the relationship between genetic polymorphism and the risk of NAFLD,and its relationship with lipid metabolism,and the correlation between serum DPP4 levels and the incidence of NAFLD.Furthermore,the pathogenesis of NAFLD is further explored from the perspective of molecular biology.Methods This study divided the DPP4 gene polymorphism test and the serum DPP4 level test by case-control study.The subjects were all from the Han population in the Qingdao area.1)According to the diagnostic criteria of NAFLD,120 NAFLD patients were selected as NAFLD group.Among the patients attending the physical examination center,151 healthy individuals were randomly selected as healthy control group.2)Two sets of blood samples were collected and submitted to Beijing Biomiao Biological Technology Co.,Ltd..,and the genotypes of DPP4 genes rs1558957,rs17848915 and rs7608798 were detected by PCR and flight mass spectrometry(MALDI-TOF MS).Laboratory indicators such as alanine aminotransferase(ALT),aspartate aminotransferase(AST),?-glutamyltransferase(GGT),fasting blood glucose(FPG),total bilirubin(TBIL),high density lipoprotein(HDL),low density lipoprotein(LDL),triglyceride(TG)and total cholesterol(TC)were detected in hospital biochemical laboratory.3)Analyze the above test results: statistically test the clinical data of the two groups and the differences of laboratory biochemical indicators;use the Hardy-Weinberg equilibrium law to analyze the genotypes of the three sites in the two groups to determine whether they have a population Representative;compare the genotypes of DPP4 gene rs1558957,rs17848915 and rs7608798 loci and the distribution of their alleles;analyze the three loci of this gene and NAFLD susceptibility and lipid metabolism.4)Screening out 88 patients with NAFLD and 88 healthy individuals.Two groups of blood samples were collected and serum DPP4 levels were measured by enzyme linked immunosorbent assay(ELISA),and TC,ALT,HDL,TG,LDL and AST were detected in hospital biochemical laboratory.5)Statistical analysis of clinical data,serum DPP4 levels and biochemical indicators differences,and analyze serum DPP4 levels and NAFLD correlation.6)All clinical information and experimental data of this paper were statistically analyzed by SPSS 25.0 software: Pearson?2 test and t test were used to compare clinical count data and measurement data respectively;binary logistic regression model analysis was used to calculate odds ratio(OR),and its 95% confidence interval(95% CI).There was a statistical difference at P <0.05.ResultsIn the test of DPP4 gene polymorphism: 1)BMI of the two groups was statistically different(P <0.05),but there was no statistical difference in gender and age(P >0.05);The ALT,GGT,TG and TC levels of the NAFLD group were higher than those of the healthy control group,and the difference was statistically significant(P <0.05).2)All three sites were in accordance with Hardy-Weinberg equilibrium law,and the genotype distribution and allele frequency of rs7608798 locus were statistically different between the two groups(P <0.05),while come to rs1558957 and rs17848915 loci,there was no significant difference in genotype distribution and allele frequency between the two group(P >0.05).3)Binary logistic regression analysis showed that the G allele of the rs7608798 locus was 1.644 times the risk than the A allele(OR = 1.644,95% CI = 1.143 to 2.367,P <0.05),while come to rs1558957 and rs17848915,there was no significant correlation between locus alleles and genotypes and NAFLD susceptibility(P >0.05).4)There was no significant correlation between polymorphisms of three sites and serum lipid levels(P >0.05).In the serum DPP4 level test: BMI of the two groups was statistically different(P <0.05),gender,age were not statistically different(P >0.05);The levels of LDL,ALT,TC,TBIL,FPG,TG,AST and GGT in healthy control group subjects were lower than those of individuals in NAFLD group(P <0.05),while its level of HDL was lower than that of healthy controls,and the difference was statistically significant(P <0.05);There was no difference in serum DPP4 levels between the two groups(P >0.05);And there was no significant correlation between DPP4 levels and the risk of NAFLD(OR = 1,95% CI = 0.999 to 1.001,P =0.949).Conclusion In the Han population of Qingdao,the allele G of the DPP4 gene rs7608798 locus is a risk factor for the pathogenesis of NAFLD,while the rs1558957 and rs17848915 locus polymorphisms are not significantly associated with the risk of NAFLD,and are not risk factors for NAFLD.There are no significant correlation serum DPP4 levels and NAFLD susceptibility.