| PART1 THE RELATIONSHIP AMONG NON-ALCOHOLIC FATTY LIVER DISEASE,METHYLENETETRAHYDROFOLATE REDUCTASE GENE(C677T)POLYMORPHISM AND HOMOCYSTEINE LEVELSObjective:(1)To analyze the relationship of Hcy level and MTHFRC677T gene polymorphism on the pathogenesis of NAFLD risk.(2)To analyze the function and interaction of MTHFRC677T gene polymorphism and NAFLD in elevated levels of Hcy.Methods:Subjects were included from January 2016 to December 2017 during the physical assessment,A total of 730 subjects were enrolled into the research:318 NAFLD patients and 412 patients without NAFLD.All subjects were from the Department of health examination in First Affiliated Hospital of Chongqing Medical University.The determination of serum Hcy levels in patients with chemiluminescent microparticle immunoassay.MTHFR detection of C677T gene polymorphism was determined by SANGER sequencing.univariate and multivariate logistic was performed to determine the association between Hcy level and MTHFR C677T gene polymorphism on the pathogenesis of NAFLD.The interaction effect between MTHFR677C/T polymorphism and NAFLD on Hcy level was analyzed by factorial analysis.The statistical analysis was performed by SAS9.4(SAS Institute Inc.,Cary,NC,USA).A value of p<0.05 was regarded as statistically significant.Results:(1)Compared to the control group,subjects of NAFLD group of Baseline data(BMI,WC,BP)biochemical indexes(?-GT?AST?ALT?WBC,TC,TG,LDL-C,FPG,UA),Hcy,FINS and HOMA-IR level was significantly higher(p<0.05)in NAFLD group;at the same time,NAFLD patients with HDL-C levels were significantly lower(p<0.05).(2)Compared to the control group,proportions of male,overweight/obesity,abdominal obesity,high blood pressure,high proportion of gamma-GT,high ALT,high AST,high WBC,high TC,high TG,high LDL-C,impaired fasting glucose and hyperuricemia were significantly higher(p<0.05),and the proportion of patients HHcy also significantly increased(p<0.05).But the different genotypes of MTHFRC677T between the two groups had no significant difference(p>0.05)(3)Compared to the control group,only MTHFRC677T(TT vs CT+CC)was statistically significant(p=0.0482)in NAFLD group,but adjusting for age,sex and NAFLD related risk factors,MTHFRC677T(TT vs CT+CC)and NAFLD was no statistically significant(p>0.05).(4)Compared to the control group,NAFLD,group had significantly higher levels of Hey(p<0.05);MTHFRC677T gene polymorphism and NAFLD had a significant interaction effect of elevated homocysteine levels(synergy)(P<0.001).Conclusions:(1)NAFLD patients are often associated with metabolic significant health problems(obesity,abnormal blood pressure,fasting blood glucose,dyslipidemia,hyperuricemia and liver enzyme abnormalities).(2)after adjustment for age,gender and NAFLD related risk factors,MTHFRC677T gene polymorphism is not associatied with the pathogenesis of NAFLD.(3)The level of Hcy was significantly higher in patients with NAFLD;at the same time,MTHFRC677T gene polymorphism and NAFLD have obvious synergistic effect on the increased level of Hcy.PART2 THE EFFECTS OF NAFLD,MTHFRC677T GENE POLYMORPHISM AND HCY ON EARLY ATHEROSCLEROSIS.Objective:(1)To analyze the clinical features of NAFLD patients with early atherosclerosis.(2)To analyze the function and interaction of NAFLD,MTHFRC677T gene polymorphism and HHcy on the brachial ankle pulse wave velocity(BaPWV)and early atherosclerosis.Methods:Subjects were included from January 2016 to December 2017 during the physical assessment,A total of 730 subjects were enrolled into the research:normal group(without arteriosclerosis and NAFLD 220),NAFLD group(NAFLD combined with early atherosclerosis)and group NAFLD+ATH(94 NAFLD with early atherosclerosis)224.All subjects were from the Department of health examination in First Affiliated Hospital of Chongqing Medical University.The determination of serum Hcy levels in patients with chemiluminescent microparticle immunoassay.MTHFR detection of C677T gene polymorphism was determined by SANGER sequencing.univariate and multivariate logistic was performed to determine the relationship between MTHFR C677T gene polymorphism and Hcy on the pathogenesis of NAFLD,BaPWV was measured by the arteriosclerosis instrument.MDR,relative excess risk due to interaction(RERI)synergy index(S)and corresponding 95%confidence interval(CI)were computed to assess the interaction effect between MTHFR677C/T polymorphism,HHcy and NAFLD on the risk of ATH.The statistical analysis was performed by SAS9.4(SAS Institute Inc.,Cary,NC,USA).A value of p<0.05 was regarded as statistically significant.Results:(1)except for age and ALT levels without increasing relationship in the control group,NAFLD group and NAFLD+AS group,the other indexes showed obvious increasing relationship between the three groups(p<0.05);chi square test showed that:male,HHcy,AO,High,AST,High y-GT High WBC,High TC,High TG,Low HDL-C,High LDL-C,High FPG,High UA and High BP ratio in the control group,NAFLD group and NAFLD+ATH group showed increased obviously(p<0.05).(2)after adjustment for age and gender case,analysis results showed that:High ?-GT(OR:1.81;95%CI:1.056?3.099),High BP(OR:5.71;95%CI:3.868?8.422),NAFLD(OR:1.90;95%CI:1.180?3.044)and HHcy(OR:1.54;95%CI:1.032?2.312)were important risk factors of ATH(p<0.05).(3)Compared to the Control group,MTHFRC677T(T vs CT+C),MTHFRC677T(TT vs CT+CC),MTHFRC677T(CTvs CC),MTHFRC677T(TT vs CC)and MTHFRC677T(CT+TT vs CC)were not significant in NAFLD group(p>0.05).(4)MDR analysis showed that the four-dimensional model(Hcy-NAFLD-BP---GT)with 75.12%the maximum test accuracy and maximum cross validation consistency(10/10),with significant statistical significance,OR value and 95%confidence interval(9.15 3.138?26.693).MTHFRC677T and NAFLD(OR:1.88;95%CI:1.075?3.290),High BP NAFLD(0R:2.34;95%CI:1.095?4.981)in ATH patients have obvious risk of multiplicative interaction;high BP and NAFLD ATH in the risk of ATH,The sum of obvious interaction,RERI(RERI:8.00;95%CI:1.373?14.625).Conclusions:(1)When patients with early atherosclerosis with NAFLD,its clinical metabolism,homocysteine levels and liver enzymology were higher.(2)After adjustment for age,sex and early atherosclerosis related risk factors,M THFRC677T gene polymorphism was not associated with early atherosclerosis incidence.(3)When HHcy,NAFLD,high BP and high y-GT existing at the same time,the interaction effects of these could increase the risk of early atherosclerosis 9.15 times.Among them,high BP and NAFLD in ATH was obviously multiply and add the risk of the interaction,the interaction of multiplicative interaction and additive interaction increased by 2.34 times and 8 times at the risk of early atherosclerosis,AP was related with in all cases the interaction can be attributed to the proportion of the case is 52%.PART3 THE EFFECTS OF NAFLD,MTHFRC677T GENE POLYMORPHISM AND HCY ON EARLY ATHEROSCLEROSISObjective:(1)To analyze the clinical features of NAFLD patients with carotid atherosclerosis(CAS).(2)To analyze the function and interaction of NAFLD,MTHFRC677T gene polymorphism and HHcy on CAS.Methods:Subjects were included from January 2016 to December 2017 during the physical assessment,A total of 730 subjects were enrolled into the research:(without carotid atherosclerosis and NAFLD)291,NAFLD(NAFLD is not associated with carotid atherosclerosis)201 NAFLD and NAFLD+CAS(NAFLD with carotid atherosclerosis)117.All subjects were from the Department of health examination in First Affiliated Hospital of Chongqing Medical University.The determination of serum Hey levels in patients with chemiluminescent microparticle immunoassay.MTHFR detection of C677T gene polymorphism was determined by SANGER sequencing,univariate and multivariate logistic was performed to determine the relationship between MTHFR C677T gene polymorphism and Hey on the pathogenesis of NAFLD.MDR,relative excess risk due to interaction(RERI)synergy index(S)and corresponding 95%confidence interval(CI)were computed to assess the interaction effect between MTHFR677C/T polymorphism,HHcy and NAFLD on the risk of CAS.The statistical analysis was performed by SAS9.4(SAS Institute Inc.,Cary,NC,USA).A value of p<0.05 was regarded as statistically significant.Results:(1)Age,SP,LDL-C,LBaPWV,RBaPWV,Hcy in subjects of NAFLD and ATH showed an upward trend(p<0.05).Through the chi square test showed that Gender(male),HHcy,High WBC,High TC,High TG,High LDL-C,High FPG,High UA,High BP and ATH ratio in the control group,NAFLD group and NAFLD+CAS group was increased obviously(p<0.05).(2)after adjusting for age and gender,HHcy(OR:1.75;95%CI:1.203?2.559),High LDL-C(OR:1.71;95%CI:1.140?2.556),ATH(OR:1.83;95%CI:1.185?2.817)were important risk factors of CAS(p<0.05)and NAFLD(OR:1.00;95%CI:0.660?1.509)was not statistically significant.(3)compared to the control group:MTHFRC677T(CT vs CC),MTHFRC677T(TT vs CC),MTHFRC677T(CT+TT vs CC)and MTHFRC677T allele(T vs C)were risk factors for CAS(p<0.05),and MTHFRC677T(TT vs CT+CC)were not statistically significant(p>0.05).(4)MDR analysis showed that the four-dimensional model(NAFLD-MTHFR677CT-HcyBaPWV)with a maximum of 68.30%testing accuracy and large cross validation consistency(8/10),with significant statistical significance,OR value and 95%confidence interval was 5.58(1.1 68?26.638);there were antagonistic interactions between NAFLD and MTHFRC677T,HHcy on the susceptibility of CAS.Conclusions:(1)Age,SP,LDL-C,LBaPWV,RBaPWV and Hey were higher in subjects of CAS patients with NAFLD.(2)after adjustment for age,sex and early atherosclerosis related risk factors,MTHFRC677T gene polymorphism in the recessive model,are associated with the pathogenesis of carotid atherosclerosis.(3)NAFLD,MTHFR677CT,HHcy and ATH coexisting could increase the risk of 5.58 times with carotid atherosclerosis risk.But there were antagonistic interactions between NAFLD and MTHFRC677T,HHcy on the susceptibility of CAS. |
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