| BackgroundThe pathogenesis of non-alcoholic fatty liver disease (NAFLD)is related to genetic-environmental- metabolic factors. NAFLD is considered as a component of metabolism syndrome (MS), which consists of obesity, type II diabetes mellitus, dyslipidemia and hypertension. NAFLD have been becoming a common cause of chronic liver diseases and transaminase abnormality. Although some epidemiological studies concerning NAFLD have been reported in China, most of them were based on clinical settings or on health check-up groups, which did not reflect population data. Adiponectin is a hormone produced by adipose tissue, and a predisposing factor of type II diabetes mellitus and MS. Plasma adiponectin is decreased in MS patients. Adiponectin gene is located in 3q27 including 3 exon and 2 intron. There are many single nucleotide polymorphisms (SNPs) in this gene. The SNPs of 45 and 276 were mostly common reported, which might be related to the susceptibility of NAFLD and MS. Prospective study in general population on this field is still lacking. In this cohort study, we followed-up people in general population in Guangdong province of southern China for 4 years in order to investigate the natural history and risk factors of NAFLD. We also investigated the relationship between SNP 45 of adiponectin gene and the subseptibility of NAFLD. Objectives:To investigate the prevalence, incidence, death causes, natural course of NAFLD, and to study the relation of changes of clinical parameters to the occurrence, progress and remission of NAFLD, and the relations of the adiponectin gene T45G polymorphisms to the susceptibility of NAFLD in population in Guangdong province.Methods:On the basis of our previously epidemiological survey of in 2005, we followed-up 3543 cases (medium 4 years), among which 624 cases were willing to receive a re-survey (re-survey group). Interview, physical examinations, biochemical tests and ultrasonography were performed again for each subject. NAFLD was diagnosed according to the criteria issued by Chinese Society of Hepatology, which was chiefly based on ultrasonographic findings. Survey for death cause was applied to all 3543 cases (death cause group). The results of natural course and the risk factors of the NAFLD development were obtained with analyzing the data from the two groups. Then the re-survey group was divided into 4 subgroups as follow:①persistent NAFLD at both baseline and endpoint (98 cases);②persistent normal at both baseline and endpoint (322 cases);③normal at baseline but NAFLD at endpoint (98 cases) ;④NAFLD at baseline but normal at endpoint (185 cases). The clinical data from subgroups①/②/③were analyzed. Subgroup was omitted from analysis, because of small sample size. PCR-RFLP was applied to detect the single nucleotide SNPs. Clinical data from three genotypes groups of adiponectin gene T45G polymorphisms were compared among subgroups②and③Results1.Natural history of NAFLDIn re-survey group of 624 cases at baseline, there were 117 cases of NAFLD, among which 51 cases (43.6%) remained unchanged, 26 (22.2%) aggravated, 21 (18.0%) alleviated and 19 (16.2%) regressed at endpoint. Among 507 normal cases at baseline, 185 cases (36.5%)developed NAFLD at endpoint. The standard prevalence of NAFLD in 2009 (22.6%) was significantly higher than that (10.5%) in 2005(P<0.05). The standard incidence was 4.9% per year.(male 5.1% vs. female 4.7%,P<0.05). The cumulative incidence rate in urban (43.1%)was significantly higher than that(27.4%) in rural areas(P<0.05). In death cause group of 3543 cases, 467 NAFLD cases at baseline were successfully followed-up, among which 4 cases (8.6‰) died of cardiovascular and cerebrovascular diseases. In 2857 normal cases successfully followed-up at baseline, 22 cases (7.7‰) died of cardiovascular/ cerebrovascular diseases and cancers. There was no significant difference between the two groups(P>0.05).2. The changes of clinical parameters in 4 year follow-upComparision of at endpoint and at baseline, in subgroup①the waist circumference, levels of fasting plasma glucose and triglyceride were significant increased, while high density lipoprotein decreased(P<0.05), in subgroup②BMI, TRIG and ALT levels were decreased(P<0.05), In subgroup③waist circumference, BMI, AST and ALT levels were remarkably increased, while HDL-C were decreased(P<0.05), in subgroup④BMI, TRIG and ALT levels were significantly decreased(P<0.05).Comparision of subgroup①and②: at endpoint, age, waist circumference, WHR, SBP, DBP, BMI, FPG, LDL-C, TRIG, CHOL, AST and ALT levels were significantly increased in subgroup①, as compared those in subgroup②(P<0.05); Single factoral analysis showed that at endpoint, waist circumference, WHR, SBP, DBP, BMI, FPG, TRIG, CHOL, AST and ALT were all risks factors of NAFLD with odds ratio (OR) values being 30.8, 10.1, 3.6, 2.8, 23.5, 2.9, 2.5, 5.5, 1.9, 4.1 and 4.2. Multivariate factoral logistic analysis showed that the increase of BMI, waist circumference TRIG and SDP were the independent risks factors of of NAFLD with OR values being 3.6, 13.3, 6.1 and 3.4.Comparision of subgroup②and③: at baseline, age, waist circumference, WHR, SBP, DBP, BMI, LDL-C levels were significantly increased in subgroup③, as compared those in subgroup②(P<0.05). Single Cox proportional hazards regression analyses showed that age, waist circumference, waist-to-hip ratio (WHR) , body mass index (BMI) and serum cholesterol levels were associated with the development of NAFLD with OR values being 1.9, 2.5, 1.4, 2.6 and 1.6(P<0.05); Multivariate regression logistic analysis showed that age and BMI were in the Cox proportional hazards regression model.Decrease of waist circumference was prone to remission.3. T45G polymorphism in exon 2 of the adiponectin gene existed in the Chinese Han people, which included there genotypes: TT, GG and GT. The adiponectin genotypes (TT:47.57% vs.50.93%,TG:45.40% vs. 42.24%,GG:7.03% vs.6.83%) and allele frequencies(T:70.27% vs. 72.05%,G:29.73% vs. 27.95%) were not significantly different between subgroup③and②( P>0.05 ) . The clinical parameters of three genotypes did not differ significantly between two groups(P>0.05).When the participants were divided into two subgroups according to their BMI abnormality, the adiponectin genotypes were also not significantly different.Conclusion:1. The prevalence and incidence of NAFLD in general population in Guangdong province of southern China were high. NAFLD was a comparatively benign disease with comparatively low death rate. The patients mainly died of cardiovascular/ cerebrovascular diseases, but not liver disease.2.Obesity, aging and dyslipidemia were all risk factors for NAFLD development.3. T45G polymorphism of the adiponectin gene existed in the Chinese people, and the development of NAFLD was not associated with adiponectin genotypes... |
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