Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is generally accepted that non-alcoholic fatty liver disease will be the most frequent liver disease in the near future and that the management of patients with non-alcoholic fatty liver disease will be a challenge for hepatologists in the next decades. Non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome, in which insulin resistance plays a crucial role. Although steatosis will often not progress to severe liver disease, in some patients, it results in cirrhosis and even hepatocellular carcinoma. Therefore, it is important to identify those patients at risk for developing fibrosis. Age, diabetes, obesity and hypertriglyceridaemia are independent risk factors for fibrosis in patients with elevated serum alanine aminotransferase levels and steatosis on ultrasound. The presence of multiple metabolic disorders increases the risk. Apart from diet, exercise and correction of underlying metabolic abnormalities, no specific treatment is available at the moment. Theoretically, thiazolidinediones are an attractive way to treat non-alcoholic fatty liver disease, because they improve insulin resistance. Some preliminary studies with thiazolidinediones were encouraging, as steatosis, inflammation and fibrosis improved in a substantial number of patients. Although no serious side effects occurred in the pilot studies, we should look vigilantly for hepatotoxicity, as the first generation thiazolidinediones proved to be toxic for the liver.
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PMID:Review article: the treatment of non-alcoholic steatohepatitis with thiazolidinediones. 1626 63

Childhood obesity is associated with a constellation of metabolic derangements including glucose intolerance, hypertension, and dyslipidemia, referred to as metabolic syndrome. The purpose of this study was to investigate genetic and environmental factors contributing to the metabolic syndrome in Hispanic children. Metabolic syndrome, defined as having three or more metabolic risk components, was determined in 1030 Hispanic children, ages 4-19 y, from 319 families enrolled in the VIVA LA FAMILIA study. Anthropometry, body composition by dual energy x-ray absorptiometry, clinical signs, and serum biochemistries were measured using standard techniques. Risk factor analysis and quantitative genetic analysis were performed. Of the overweight children, 20%, or 28% if abnormal liver function is included in the definition, presented with the metabolic syndrome. Odds ratios for the metabolic syndrome were significantly increased by body mass index z-score and fasting serum insulin; independent effects of sex, age, puberty, and body composition were not seen. Heritabilities +/- SE for waist circumference, triglycerides (TG), HDL, systolic blood pressure (SBP), glucose, and alanine aminotransferase (ALT) were highly significant. Pleiotropy (a common set of genes affecting two traits) detected between SBP and waist circumference, SBP and glucose, HDL and waist circumference, ALT and waist circumference, and TG and ALT may underlie the clustering of the components of the metabolic syndrome. Significant heritabilities and pleiotropy seen for the components of the metabolic syndrome indicate a strong genetic contribution to the metabolic syndrome in overweight Hispanic children.
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PMID:Quantitative genetic analysis of the metabolic syndrome in Hispanic children. 1630 1

The present study attempted to establish whether elevated serum levels of alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) are independent (of each other) markers of systemic inflammation and oxidative stress as assessed by the plasma levels of C-reactive protein (CRP) and lipid peroxides (lipOX), regardless of the presence of underlying metabolic syndrome (as defined by the modified Adult Treatment Panel III (ATPIII) criteria). The plasma levels of CRP and lipOX were determined in 1483 middle-age Japanese men (42+/-9 years). A general linear model analysis indicated that elevated serum ALT and/or serum GGT (levels in the respective highest quartiles) were significantly related to the logarithms of the plasma levels of CRP (Beta=0.08 (0.05-0.11) and 0.08 (0.05-0.11), respectively) and the logarithm of the plasma levels of lipOX (Beta=0.03 (0.01-0.05) and 0.03 (0.01-0.05), respectively), regardless of the presence of underlying metabolic syndrome (MetS) (p<0.01). In addition, the presence of MetS and elevated serum levels of both of these liver enzymes additively increased the plasma levels of CRP and lipOX. Thus, it is proposed that elevated serum ALT and elevated serum GGT are independent markers of the activation of systemic inflammation and increased oxidative stress, independent of their relationship to MetS, and that the presence of MetS and elevations of both of these liver enzymes may additively worsen the atherogenic state.
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PMID:Elevated serum levels of alanine aminotransferase and gamma glutamyltransferase are markers of inflammation and oxidative stress independent of the metabolic syndrome. 1640 92

We previously reported that the prevalence of elevated alanine aminotransferase (ALT) increases with accumulation of metabolic syndrome components, and a greater degree of involvement of aldehyde dehydrogenase 2 (ALDH2) than beta3-adrenergic receptor gene (beta3-AR) polymorphisms. The present study was designed to clarify the effect of aging, lifestyle and the two gene polymorphisms on the relationship between 4 components of the metabolic syndrome (obesity, hypertension, dyslipidemia and impaired glucose tolerance) and elevated ALT values in a subset of 73 out of 148 male workers who were 35 years of age in the baseline study and 40 years old in the present study. Study subjects completed questionnaires about drinking and smoking habits, and underwent urinalysis, physical examination and peripheral blood tests, blood chemistry, electrocardiogram and chest X-rays each year as required by Japanese law. Information from the questionnaires and physical examinations, including liver function tests, were compared with previously reported ALDH2 and beta3-AR genotypes for the 73 workers. Of the 73 workers studied, 14 (19%) demonstrated decrease in metabolic syndrome components, 39 (53%) demonstrated no change, and 20 (27%) demonstrated an increase. Ten workers (14%) showed liver dysfunction at age 35 and 20 workers (27%) at age 40. Fourteen workers were newly diagnosed as having liver dysfunction at their 40-year checkup, thus being associated with the BMI and an active ALDH2 genotype. Accumulation of components of the metabolic syndrome were associated with the presence of liver dysfunction at 35 years. In conclusion, these findings indicate that ALDH2 genotyping as well as lifestyle habits may be important factors in causing metabolic syndrome with liver dysfunction.
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PMID:Change of components of the metabolic syndrome in a workers' health checkup after five years--relation with elevated liver enzymes, gene polymorphisms for ALDH 2, beta3-AR and lifestyle. 1640 83

The prevalence of obesity is particularly high in Black and Latino pediatric populations. A limited number of metabolic studies suggest that race plays a role in the development of obesity-related co-morbidities. We evaluated clinical and metabolic characteristics of 428 obese (mean BMI z-score 2.63) children and adolescents ranging in age from 2-20 years, of primarily Dominican ancestry attending the obesity clinic at Children's Hospital of New York Presbyterian over a 5-year period (1998-2003). Of 193 patients available for detailed metabolic analysis, abnormalities were found for elevated systolic blood pressure (19%), diastolic blood pressure (11%), total cholesterol (18%), LDL (12%), triglycerides (10%), AST (<1%), ALT (4%), low HDL (47%), impaired fasting glucose (5%), impaired glucose tolerance 7%, diabetes mellitus by fasting criteria(<1%), and metabolic syndrome (14%). Despite extraordinary family histories of obesity and diabetes mellitus, the metabolic syndrome and abnormalities of glucose regulation were relatively infrequent compared to studies of obese, pediatric Latino patients of primarily Mexican and Puerto Rican ancestry. This finding suggests that Latinos from different areas of origin may have different risks of obesity-related conditions.
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PMID:Clinical and metabolic characteristics of an obese, Dominican, pediatric population. 1645 52

The biochemical differences between simple steatosis, a benign liver disease, and non-alcoholic steatohepatitis, which leads to cirrhosis, are unclear. Fat aussie is an obese mouse strain with a truncating mutation (foz) in the Alms1 gene. Chow-fed female foz/foz mice develop obesity, diabetes, and simple steatosis. We fed foz/foz and wildtype mice a high-fat diet. Foz/foz mice developed serum ALT elevation and severe steatohepatitis with hepatocyte ballooning, inflammation, and fibrosis; wildtype mice showed simple steatosis. Biochemical pathways favoring hepatocellular lipid accumulation (fatty acid uptake; lipogenesis) and lipid disposal (fatty acid beta-oxidation; triglyceride egress) were both induced by high-fat feeding in wildtype but not foz/foz mice. The resulting extremely high hepatic triglyceride levels were associated with induction of mitochondrial uncoupling protein-2 and adipocyte-specific fatty acid binding protein-2, but not cytochrome P4502e1 or lipid peroxidation. In this model of metabolic syndrome, transition of steatosis to steatohepatitis was associated with hypoadiponectinemia, a mediator of hepatic fatty acid disposal pathways.
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PMID:Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice. 1651 52

Several studies have reported an association between markers of liver injury, including elevated concentrations of alanine aminotransferase (ALT) aspartate aminotransferase (AST), and prospective risk of type 2 diabetes. We therefore examined the relationship between ALT and AST on the one hand, and serum adiponectin and highly sensitive CRP on the other, both of which have been reported to be associated with prospective risk of type 2 diabetes; we also tested for variable components of metabolic syndrome in 198 male college students aged 18-20 years. ALT showed a positive relationship with percentage body fat (r = 0.19, p = 0.02), serum leptin (r = 0.21, p = 0.01), LDL cholesterol (r = 0.29, p = 0.0003), triglyceride (r = 0.28, p = 0.0004) and apolipoprotein B (r = 0.35, p < 0.0001) even after adjustment for body mass index (BMI). Although there was a significant relationship with serum insulin, adiponectin (inversely), homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure, HDL cholesterol (inversely) and LDL particle diameter in simple regression analysis, significance disappeared after adjustment for BMI. In contrast, CRP (r = 0.16, p = 0.04) was associated with ALT after adjustment for BMI, although simple regression analysis revealed no association between the two. Relationships were smaller for AST, and significance disappeared after adjustment for BMI. Multiple regression analysis excluding lipid variables revealed significant and independent associations of ALT with adiponectin and percentage body fat. In a model including lipid variables, apolipoprotein B emerged as an independent predictor of ALT in addition to adiponectin and percentage body fat. These variables explained 29 % of ALT variability. In conclusion, serum ALT levels were associated with leptin and CRP as well as many components of the insulin resistance syndrome in young healthy men. Adiponectin, apolipoprotein B and percentage body fat emerged as significant and independent predictors of ALT. Since adiponectin and chronic subclinical inflammation have been reported to predict the development of type 2 diabetes and since abnormalities in apolipoprotein B metabolism occur in the early course of insulin resistance, these findings may be compatible with the association between liver markers and risk of diabetes.
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PMID:Serum alanine aminotransferase is associated with serum adiponectin, C-reactive protein and apolipoprotein B in young healthy men. 1652 13

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that has been shown to progress to cirrhosis and hepatocellular carcinoma. This article reviews the prevalence of NAFLD and the factors associated this disorder, and with the more advanced stages of NAFLD, including nonalcoholic steatohepatitis (NASH) and fibrosis. In the general population, the estimated prevalence ranges from 3% to 24%, with most estimates in the 6% to 14% range. NAFLD is extremely common among patients undergoing bariatric surgery, ranging from 84% to 96%. In these patients, 25% to 55% have NASH, 34% to 47% have fibrosis, and 2% to 12% have bridging fibrosis or cirrhosis. NAFLD appears to be most strongly associated with obesity, and insulin resistance states including diabetes and with other features of the metabolic syndrome, such as high triglycerides and low HDL. It appears to be more common in men, and it increases with increasing age and after menopause. Some data suggest that Mexican Americans are more likely to have NAFLD and blacks are less likely compared with non-Hispanic whites. More advanced stages of NAFLD are associated with older age, higher body mass index, diabetes, hypertension, high triglycerides, and/or insulin resistance. An AST/ALT ratio greater >1 may also indicate more severe disease. Although hepatocellular carcinoma can occur in the setting of NAFLD, the risk factors for hepatocellular carcinoma in the setting of NAFLD have not been established. More prospective studies are needed to determine the true risk factors for the development and progression of NAFLD to help identify patients at highest risk who might benefit from treatment trials.
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PMID:The epidemiology of nonalcoholic fatty liver disease in adults. 1654 Jul 68

Nonalcoholic fatty liver disease is a common condition associated with metabolic syndrome. It is the most common cause of elevated liver enzymes in U.S. adults, and is diagnosed after ruling out other causes of steatosis (fatty infiltration of liver), particularly infectious hepatitis and alcohol abuse. Liver biopsy may be considered if greater diagnostic and prognostic certainty is desired, particularly in patients with diabetes, patients who are morbidly obese, and in patients with an aspartate transaminase to alanine transaminase ratio greater than one, because these patients are at risk of having more advanced disease. Weight loss is the primary treatment for obese patients with nonalcoholic fatty liver disease. Medications used to treat insulin resistance, hyperlipidemia, and obesity have been shown to improve transaminase levels, steatosis, and histologic findings. However, no treatments have been shown to affect patient-oriented outcomes.
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PMID:Nonalcoholic fatty liver disease. 1677 Sep 27

For a long time, hepatic steatosis was believed to be a benign condition. Only recently, liver steatosis, also termed non-alcoholic fatty liver disease (NAFLD), has gained much interest. In most cases of NAFLD, a condition regarded as the hepatic component of the metabolic syndrome, the enzyme alanine aminotransferase (ALT) is elevated and consequently has been used as a marker for NAFLD. More recently, several cross-sectional and prospective studies have demonstrated associations of this liver enzyme with features of the metabolic syndrome and type 2 diabetes mellitus. This review discusses the biochemical and metabolic properties of ALT, its applicability as a marker of NAFLD and describes its possible role in the pathogenesis of the metabolic syndrome and type 2 diabetes mellitus and subsequent cardiovascular disease. In addition, treatment strategies to ameliorate NAFLD and the associated risks are discussed.
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PMID:Alanine aminotransferase as a marker of non-alcoholic fatty liver disease in relation to type 2 diabetes mellitus and cardiovascular disease. 1682 76


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