Association Of Gene Polymorphism In Promoter Region Of Pigment Epithelium-derived Factor And Non-alcoholic Fatty Liver Disease In Patients With Type2Diabetes Mellitus

Objective To investigate relationship between serum pigment epithelium-derivedfactor level, gene polymorphism in promoter region-358G→A and non-alcoholic fattyliver disease(NAFLD) in type2diabetes mellitus(T2DM) of Fujian Han．Methods294T2DM patients with the similar proportion of age and gender weredivided into two groups：DM1group (with non-alcoholic fatty liver disease,n=190)and DM2(without non-alcoholic fatty liver disease,n=104).Serum pigmentepithelium-derived factor(PEDF) level, fasting plasma glucose (FPG), fasting insulin(FINS), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG),low density lipoprotein (LDL-C), high density lipoproteins (HDL-C), body height,weight, waist circumference (WC), hip circumference (HC), systolic blood pressure(SBP), diastolic blood pressure (DBP) and carotid artery intima media thickness(CIMT) were measured. Body mass index (BMI), waist to hip ratio (WHR) andhomeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Thepigment epithelium-derived factor gene SNP-358G→A polymorphism was identifiedby polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).The Hardy-Weinberg equilibrium was tested. The genotype and allele frequencies ofDM1groups were compared with that of DM2groups. Two groups were compared byT text, Chi-square test or rank-sum test.Correlation analysis was test by unconditionedbinary classification of logistic regression analysis. Relative risk degree was showedby odds ratio and95%CI.Results (1) Comparison of clinical and biochemical parameters between DM1groupand DM2group: DM1group has much higher levels of PEDF,WC, HC, WHR, DBP,ALT, TG, FINS, HOMA-IR, HbA1c and CIMT, but lower HDL-C (P<0.05). (2) Logistic regression analysis on risk factors of NAFLD in T2DM revealed thatPEDF level,WC, DBP, ALT, TG and HDL-C were independent factors.(3) Thefrequencies of PEDF gene-358G→A genotype (GG genotype, GA genotype and AAgenotype) and allele (G/A) showed the significant difference between DM1and DM2group (P<0.05).(4) In the PEDF gene SNP-358G→A allele, GA genotype carrierssuffering NAFLD Was2.085times of that of GG genotype；GA and AA genotypecarriers suffering NAFLD Was2.080times of that of GG genotype。(5) BMI, WHR,DBP, AST, ALT, TG, FINS, HOMA-IR and CIMT were higher in GA and AAgenotype than that inGG genotype, otherwise, PEDF level, HDL-C were higher inGG genotype than that in GA and AA genotype (P<0.05).Conclusion Serum pigment epithelium-derived factor level was the independentfactor of NAFLD in T2DM.PEDF level of DM1group was much higher than that ofDM2group. Elevation of Serum PEDF was the response of insulin resistance, whichcan improve the effect of insulin resistance and prevent insulin sensibility. In T2DMpatients the-358G→A polymorphism of the PEDF gene were in association withNAFLD, which suggested that carriers of the A allele gene had a higher risk ofsuffering NAFLD.