AIM:To investigate the population-based prevalence of fatty liver disease (FLD) and its risk factors in Guangdong Province, China. METHODS:A cross-sectional survey with multiple-stage stratified cluster and random sampling of inhabitants over 7-year-old was performed in 6 urban and rural areas of Guangdong Province, China. Questionnaires, designed by co-working of epidemiologists and hepatologists, included demographic characteristics, current medication use, medical history and health-relevant behaviors, i.e., alcohol consumption, smoking habits, dietary habits and physical activities. Anthropometric measurements, biochemical tests and abdominal ultrasonography were carried out. RESULTS:Among the 3543 subjects, 609 (17.2%) were diagnosed having FLD (18.0% males, 16.7% females, P > 0.05). Among them, the prevalence of confirmed alcoholic liver disease (ALD), suspected ALD and nonalcoholic fatty liver disease (NAFLD) were 0.4%, 1.8%, and 15.0%, respectively. The prevalence rate (23.0%) was significantly higher in urban areas than (12.9%) in rural areas. After adjustment for age, gender and residency, the standardized prevalence of FLD in adults was 14.5%. Among them, confirmed ALD, suspected ALD and NAFLD were 0.5%, 2.3%, and 11.7%, respectively, in adults and 1.3% (all NAFLD) in children at the age of 7-18 years. The overall prevalence of FLD increased with age in both genders to the peak of 27.4% in the group of subjects at the age of 60-70 years. The prevalence rate was significantly higher in men than in women under the age of 50 years (22.4% vs 7.1%, P < 0.001). However, the opposite phenomenon was found over the age of 50 years (20.6% vs 27.6%, P < 0.05). Multivariate and logistic regression analysis indicated that male gender, urban residency, low education, high blood pressure, body mass index, waist circumference, waist to hip ratio, serum triglyceride and glucose levels were the risk factors for FLD.CONCLUSION: FLD, especially NAFLD, is prevalent in South China. There are many risk factors for FLD.

Background and Aim: The aim of this study was to investigate the influence of polygenetic polymorphisms, which play a role in the pathogenesis of metabolic syndrome, on the susceptibility to non-alcoholic fatty liver disease (NAFLD) of Chinese people. Methods: The subjects were selected from an epidemiological survey in the Guangdong province of southern China. In each polymorphism study, 50-117 subjects who met the diagnostic criteria of NAFLD and had typical clinical and ultrasonographic findings were placed into the case group. Using a nested case-control design, the same numbers of matched people without NAFLD were included as controls. Single nucleotide polymorphisms (SNP) at nine positions in seven candidate genes were tested. These SNP were found to be associated with the pathogenesis of metabolic syndrome. Genetic analyses were performed using genomic DNA extracted from peripheral blood leukocytes. Polymerase chain reaction-restriction fragment length polymorphism was applied to detect SNP. Results: Most candidate genes' SNP were associated with susceptibility to NAFLD. Some showed positive relationships (increased risk): tumor necrosis factor-a-238, adiponectin-45, leptin-2548, peroxisome proliferator-activated receptors-161 and phosphatidylethanolamine N-methyltransferase-175. Other SNP demonstrated a negative association (decreased risk): adiponectin-276 and hepatic lipase-514. Only two were not associated: tumor necrosis factor-a-380 and peroxisome proliferator-activated receptors-g coactivator-1a-482. Conclusion: Most candidate genes' SNP examined in metabolic syndrome patients were associated with susceptibility to NAFLD.

Acetaminophen overdose is a leading cause of drug-related acute liver failure in the United States. Glutathione, a tripeptide antioxidant protects cells against oxidative damage from reactive oxygen species and plays a crucial role in the detoxification of xenobiotics, including acetaminophen. Glutathione is synthesized in a two-step enzymatic reaction. Glutamate-cysteine ligase carries out the rate-limiting and first step in glutathione synthesis. We have generated C57Bl/6 mice that conditionally overexpress glutamate-cysteine ligase, and report here their resistance to acetaminophen-induced liver injury. Indices of liver injury included histopathology and serum alanine aminotransferase activity. Male transgenic mice induced to overexpress glutamate-cysteine ligase exhibited resistance to acetaminophen-induced liver injury when compared with acetaminophen-treated male mice carrying, but not expressing glutamate-cysteine ligase transgenes, or to female glutamatecysteine ligase transgenic mice. We conclude that glutamatecysteine ligase activity is an important factor in determining acetaminophen-induced liver injury in C57Bl/6 male mice. Because people are known to vary in their glutamate-cysteine ligase activity, this enzyme may also be an important determinant of sensitivity to acetaminophen-induced liver injury in humans.The tripeptide antioxidant glutathione (GSH; ␥-glutamylcysteinylglycine) is one of the most abundant cellular thiols. It protects cells against oxidative damage from reactive oxygen species, maintains cellular redox status, promotes cell growth, and plays a crucial role in the detoxification of xenobiotics. GSH can directly scavenge free radicals, act as an antioxidant in GSH-mediated reduction of peroxides and act as a co-substrate for glutathione S-transferase-mediated detoxification of reactive intermediates formed during phase I metabolism (1).GSH plays a major role in detoxifying many hepatotoxicants including acetaminophen (APAP), 3 an over-the-counter analgesic and antipyretic (2-5). APAP overdose is responsible for nearly 50% of the acute liver failure cases in the United States (6) and is thus of high public health concern. APAP metabolism has been well defined, making it a good model for drug-induced liver toxicity. APAP is primarily metabolized through sulfation and glucuronidation pathways (7-9). However, a fraction of APAP is bioactivated by cytochrome P-450s to n-acetyl-p-benzoquinoneimine (NAPQI), which can bind to cellular proteins (3, 7, 10 -12). NAPQI also covalently binds to GSH and is either converted back to APAP, or forms the non-toxic APAP-GSH conjugate. APAP overdose results in depletion of hepatic GSH (by as much as 90%) (2). As GSH stores are depleted, increased levels of NAPQI-protein adducts form, and such adducts are thought to be an important contributor to APAP hepatotoxicity (3,7,8,10,11).Pretreatment with N-acetylcysteine (7, 9, 10), a source of cysteine for GSH biosynthesis, attenuates APAP-induced hepatotoxicity. N-Acetylcysteine given soon after APAP (within...

The early determination of family for a newly found enzyme molecule becomes important because it is directly related to the detail information about which specific target it acts on, as well as to its catalytic process and biological function. Unfortunately, it is still a hard work to distinguish enzyme classes by experiments. With an enormous amount of protein sequences uncovered in the genome research, it is both challenging and indispensable to develop an automatic method for fast and reliably classifying the enzyme family. Using the concept of Chou's pseudo amino acid composition, we developed a new method that coupled discrete wavelet transform with support vector machine based on the amino acid hydrophobicity to predict enzyme family. The overall success rate obtained by the 10-cross-validation for the identification of the six enzyme families was 91.9%, indicating the current method could be an effective and promising high-throughput method in the enzyme research.