| Background:Fatty liver disease(FLD) also called fatty liver,is a clinical pathological syndrome caused by a variety of causations.The lesion of FLD mainly lies in liver foliole,and it is characterized as triglycerides accumulation superfluously in hepatocytes.In recent years,with the improvement of people's lives and the change of diet structure,the incidence rate of FLD has further increased.According to statistics, in the correction of age,sex and residential area,and other factors,the standard incidence rate of FLD,alcoholic fatty liver disease(alcoholic fatty liver disease,AFLD) and non-alcoholic fatty liver(nonalcoholic fatty liver disease,NAFLD) were 11.3%,2.2%and 9.1%separately(in adult,they were 14.5%,2.9%and 11.7% separately),so the incidence rate of FLD has the growing trend beyond viral hepatitis.In addition,FLD may lead to liver-related disability and deaths,which has become a global medical issues of common concern and social problems.Fatty liver disease is the result of a variety of factors interaction.At present,the relationships between apoptotic factors and hepatocyte steatosis aroused the concern by many scholars.Tumour necrosis factor(TNF)-related apoptosis inducing ligand(TRAIL) was found and named by Wiley in 1995,TRAIL is mapped to the long arm of chromosome 3q26 in humans and is composed of five exons.It encodes approximately 1.77 kb mRNA,32.5 KDa transmembrane(typeⅡ) glycoprotein composed of 281 amino acid.TRAIL belongs to TNF-super family,and its structure is similar to other TNF family members.By combining with its receptor,TRAIL can induce apoptosis or play other biological effects.It has been reported that levels of TRAIL are related to lipid levels of human peripheral blood.In recent years,it is found that TRAIL can induce hepatocyte steatosis after virus infection and after alcohol intaking.However,the mechanism of TRAIL involved in FLD is unclear.It is believed that the occurrence of FLD are related to polymorphisms of many apoptotic factors,but reports on the relation between FLD and TRAIL polymorphisms have not been appeared in the literature.Objective:To observe the serum concentration of soluble TRAIL(sTRAIL), aminotransferase,Glucose,lipid among NAFLD,AFLD,healthy controls and excessive drinking controls without liver disease.To observe the polymorphism and gene frequency of TRAIL gene 1525G/A and 1595C/T of the 3'-UTR in Chinese Han nationality population.To further explore the association of TRAIL polymorphism with susceptibility to fatty liver.Methods:This study followed a case-control design.A total of 163 FLD subjects(84 NAFLD and 79 AFLD) were analyzed according to generally accepted diagnosis criteria for example B ultrasonic.102 healthy blood donors(80 healthy controls and 22 excessive drinking controls without liver disease) were used as controls.All targets were chosen fasting.The levels of sTRAIL in serum were determined by ELISA(44 NAFLD patients and 35 healthy controls).The polymorphisms of TRAIL gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 80 patients of alcohol fatty liver disease,79 patients of nonalcoholic fatty liver disease,80 healthy controls and 22 healthy controls with alcohol.At the same time,we selected 10 samples to sequence randomly in order to validate the foregoing of PCR-RFLP results.Results:(1) The NAFLD group showed significantly higher levels of sTRAIL in serum than those of healthy control group(p=0.017,p＜0.05);(2) Serum sTRAIL concentrations positively correlated with triglyceride(TG) significantly(r=0.368,P =0.014,P＜0.05).(3)There were TRAIL gene 1525G/A,1595C/T polymorphisms in Chinese Hans.(4)The same mutation happened at position 1525,1595 in exon 5 of TRAIL gene in 265 Chinese Han.(5) The genotype distributions among NAFLD, AFLD and healthy control(without alcohol) were significantly different(p=0.016,p ＜0.05;p=0.013,p＜0.05);1525G allele and 1595C allele were more frequent in FLD patients than in controls(without alcohol)(p=0.017,p＜0.05).(6) In NAFLD patients,the TG concentration of individuals with GG/CC genotype at 1525/1595 was higher than that of AA/TT genotype(p=0.035,p＜0.05).(7) The serum concentration of alanine aminotransferase(ALT),aspartate aminotransferase(AST), glutamyl transpeptidase(GGT),blood Glucose(GLU),cholesterol(CH),TG in NAFLD group were higher than those in healthy control(without alcohol),the differences were statistically significant(p＜0.05).(8) The serum concentration of ALT,GLU,CH,TG in AFLD group were higher than those in excessive drinking controls without liver disease(p＜0.05).(9) The serum concentrations of ALT,AST, GGT,GLU,CH,TG in AFLD group were higher than those in healthy control(without alcohol)(p＜0.05).(10) Obesity,hyperlipidemia,High level of GGT are risk factors of NAFLD by Non-conditions more Logistic regression analysis.Conclusion:The PCR-RFLP can detect the TRAIL genotype accurately.There are TRAIL gene 1525G/A,1595C/T polymorphisms in Chinese Hans.(1) The study indicated that sTRAIL concentrations in serum were related to hepatic steatosis and sTRAIL concentrations were positively correlated with TG concentrations.(2)The results showed Chinese Hans people with alleles 1525G,1595C in the 3'-UTR of exon 5 of TRAIL are susceptibility to FLD.(3) There is the same genetic variation of TRAIL at position 1525G/A and 1595C/T in Chinese populations.Some nearby polymorphic loci tend to with the common genetic,and it is one type of haplotype.(4) People with GG/CC genotype at 1525/1595 sites of TRAIL are susceptible to high blood lipid.(5) Obesity,hyperlipidemia,High level of GGT are risk factors of NAFLD. |
