The Relationship Between The Polymorphism Of Transforming Growth Factor-betal -509 C/T And Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) includs simple fatty liver(SFL),non-alcoholic steatohepatitis(NASH) and related cirrhosis.Study found the level of TGF-β1 in fatty liver patients'peripheral blood obviously increased and related to the severity of the disease.Many polymorphisms of TGF-β1 gene have been idetified including which was localized in the promoter region at psitions -509C>T upstream of 1exon and related to various diseases. It needs to be comprehensively studied about the influence of polymorphisms of TGF-β1 gene on TGF-β1 plasma concentration.Based on all above,we detected the polymorphism at psitions -509C>T in the promoter region of TGF-β1 gene and further studied the association of the polymorphism with NAFLD in Shanxi Populations. PartⅠThe study of relationship between the polymorphism of transforming growth factor-beta1 509 C/T and non-alcoholic fatty liver diseaseObjective To explore the relationship between the polymorphism of C-509T at the promoter region of transforming growth factor(TGF)β1 gene and non- -alcoholic fatty liver disease(NAFLD).Methods A polymerase chain reaction-restri- -ction fragment length polymorphism(PCR-RFLP) was established to detect TGFβ1 genotypes.Results①There were no significant differences in the frequencies of TGFβ1-509C/T gene between the patients and control group(p>0.05).②The CT genotype prevailed in both the SFL and the NASH patients.The frequency of CC genotype (27.4%)was higher than that of TT genotype(19.2%) in NASH patients while the frequency of TT genotype(21.6%) was higher than that of CC genotype(4.1%) in SFL patients.There were significant differences between all the groups(p<0.05).③In stratified analysis on the basis of sex,the frequencies of genotypes and alleles were significantly different (genotype:P<0.05;allele:P<0.01) in the male subjects,but no difference in the female subjects. Conclusion No evident association was found between TGFβ1-509C/ T polymorphism and NAFLD,but the presence of C allete at position -509 may play an important role in the progression of NAFLD,and male subjects with -509C/T variant of TGFβ1 were more facilitated to develop NAFLD.PartⅡThe study of relationship between the polymorphism of transforming growth factor beta1 -509 C/T and TGF-β1 plasma concentrationObjective To detect TGF-β1 plasma concentration and explore it's relationship with the polymorphism of C-509T at the promoter region of TGF-β1.Methods In this Part,the concentrations of total TGFβl,IL-10 were measured in plasma by ELISA.Results①Compared to control group,TGF-β1 plasma concentrations were higher in NAFLD group and IL- 10 level was lower(p<0.05). The concentration of TGFβl was not closely related to HDL-C,LDL-C,TG,FPG.However,there was significant relationship between TGF-β1 and ALT (r=0.66 , p=0.009),TGF-β1 and IL-10(r=-0.54 , p=0.031).②The TGF-β1 plasma concentrations were statistieally higher in subjects with CC and CT genotype than in those with TT genotype in NAFLD group(P<0.001),but the concentrations did not show any difference in there genotypes in control group.③In both control group and NAFLD group, LDL-C, FINS, TG,HOMA-IR were significant higher in CC and CT genotype subjects than that in TT genotype subjects(P<0.05), HDL-C was significant lower in CC and CT genotype subjects than that in TT genotype subjects(P<0.01). Conclusion①The levels of TGF-β1 and IL-10 have clinical value in the pathologic mechanism of causes NAFLD.②TGFβ1-509C/T polymorphism is close associated with TGF-β1 plasma concentration in NAFLD group.③TGFβ1-509C/T polymorphism was regarded to be latently at risk of the metabolic syndrome.