Correlation Between Dietary Fatty Acid,CES1 Gene Copy Number Variation And Non-alcoholic Fatty Liver Disease

Objective(1)To explore the relationship between the daily intake of dietary fatty acids and non-alcoholic fatty liver disease(NAFLD)among medical examiners in Nanping City.(2)To examine the effect of omega-3 polyunsaturated fatty acid(?-3 PUFA)supplementation on NAFLD.(3)To compare the distribution of CES1 gene copy number variation(CNV)between case and control groups,analysis the relationship between CES1 CNV and its serum level and the risk of NAFLD.This study will provide substantial evidence on the prevention and treatment of NAFLD and provide new clues to elucidate its genetic susuceptibility.Methods(1)A hospital-based case-control study was conduct and a Semi-quantitative Food Frequency Questionnaire(SQFFQ)was administered amoung the collected cases and controls.The daily average dietary fatty acid intake was calculated according to the “Chinese Food Composition Table”(2009 Revision).Participants were grouped and assigned 1,2,3,4 in order according to the quantitative quartiles of intakes of control group.Unconditional logistic model was applied to explore the role of dietary fatty acids in the risk of NAFLD.(2)Meta analysis was conducted.Literature search strategies,inclusion and exclusion criteria were setted.Literature quality was evaluated,data was extracted.The data was pooled using random-effect or fixed-effect models.(3)Peripheral blood samples were collected from patients and controls.TaqMan? probe-based real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay(ELISA)methods were used to detect the CES1 CNV and serological level.And unconditional logistic model was applied to explore the relationship between CES1 CNV and serum expression level and the risk of NAFLD.Results(1)After total energy adjusted multivariate logistic regression analysis showed that high intakes of total FA(Q2,Q3,Q4),SFA(Q3),MUFA(Q3,Q4),PUFA(Q3,Q4),plant-derived FA(Q3,Q4),?-6 PUFA(Q3,Q4)and high ratio of ?-6/?-3 PUFA(Q3,Q4)can increase the risk of NAFLD by about 0.58-6.72 times.And statistically significant results were more easily observed in paiticipants of women and 40-60 years old.(2)Meta-analysis showed that ?-3 PUFAs can significantly improve liver fat,ALT,AST,GGT,TG,IR and glucose in patients with NAFLD.The pooled effects were: RR = 1.49(95% CI: 1.24,1.80),SMD =-0.61(95% CI:-0.97,-0.24),SMD =-0.66(95% CI:-1.14,-0.18),SMD =-0.48(95% CI:-0.70,-0.25),SMD =-0.51(95% CI:-0.81,-0.21),WMD =-0.41(95% CI:-0.59,-0.23),SMD =-0.26(95% CI:-0.44,-0.08).(3)Multivariate logistic regression analysis showed that loss of CES1 gene copy number was significantly associated with a greater risk of NAFLD,OR = 2.17(95% CI: 1.06,4.46).Stratified analysis showed that loss of CES1 gene copy number in female participants was significantly associated with a greater risk of NAFLD OR = 3.79(95% CI: 1.17,12.29).The relationship between loss of CES1 gene copy number and risk of NAFLD in male participants did not reach statistical significance.There was no statistical correlation between serum CES1 level and NAFLD.Conclusions(1)Excessive intake of FA including SFA,MUFA,PUFA,?-6 PUFA,and high ?-6/?-3 PUFA ratio is a risk factor for NAFLD.(2)?-3 PUFA supplementatiom can decrease liver fat,ALT,AST,GGT,TG,IR and glucose.(3)CNV loss in CES1 gene was a risk factor for NAFLD in female.