Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormal liver tests, as well as morphological changes in the liver, are frequent among obese patients. Other frequent disturbances are visceral fat accumulation, insulin resistance, non-insulin-dependent diabetes mellitus (NIDDM), hypertriglyceridemia, and hypertension; these are set of aberrations known as the metabolic syndrome. In order to investigate a possible relationship between the metabolic syndrome and impaired liver status we examined associations between liver tests, metabolic variables (insulin, glucose, and triglycerids), body composition and nutrition in 1,083 men (BMI 28.8-63.8 kg/m2) and 1,367 women (BMI 26.7-68.0 kg/m2) in the ongoing intervention study of Swedish Obese Subjects (SOS). Standard biochemical techniques were used to assess liver status and metabolic variables. Lean body mass (LBM) and masses of visceral and subcutaneous adipose tissue (AT) were estimated by means of computed tomography (CT) calibrated anthropometric equations. In both genders aspartate aminotransferase and alanine aminotransferase were, or tended to be, positively correlated to fasting serum insulin, visceral AT (women), and alcohol intake. In women, the aminotransferases were also correlated with fasting blood glucose. In both genders alkaline phosphatase was, or tended to be, positively associated with visceral AT, insulin (women), and glucose. Bilirubin was negatively correlated to insulin and visceral AT in men and women. Additional multivariate analyses indicated that alcohol had less explanatory power than serum insulin for the examined liver tests, especially among women. These results suggest that pathological liver tests in the obese may represent an expression of the metabolic syndrome.
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PMID:Are elevated aminotransferases and decreased bilirubin additional characteristics of the metabolic syndrome? 911 45

Chronic liver disease is a major cause of morbidity and mortality in the United States. Although often used to detect liver disease, the prevalence and etiology of elevated aminotransferases are unknown. We analyzed data on adults ages 17 yr and older (N = 15,676) from the Third National Health and Nutrition Examination Survey (1988-1994). Participants were classified as having elevated aminotransferase levels if either aspartate aminotransferase or alanine aminotransferase was elevated above normal. Aminotransferase elevation was classified as "explained" if there was laboratory evidence of hepatitis B or C infection, iron overload, or if there was a history of alcohol consumption. Analyses were weighted to provide national estimates. The prevalence of aminotransferase elevation in the United States was 7.9%. Aminotransferase elevation was more common in men compared to women (9.3% vs 6.6%, p = 0.002), in Mexican Americans (14.9%) and non-Hispanic blacks (8.1%) compared to non-Hispanic whites (7.1%, p < 0.001). High alcohol consumption, hepatitis B or C infection and high transferrin saturation were found in only 31.0% of cases. Aminotransferase elevation was unexplained in the majority (69.0%). In both men and women, unexplained aminotransferase elevation was significantly associated with higher body mass index, waist circumference, triglycerides, fasting insulin, and lower HDL; and with type 2 diabetes and hypertension in women (all p < 0.05). Aminotransferase elevation was common in the United States, and the majority could not be unexplained by alcohol consumption, viral hepatitis or hemochromatosis. Unexplained aminotransferase elevation was strongly associated with adiposity and other features of the metabolic syndrome, and thus may represent nonalcoholic fatty liver disease.
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PMID:The prevalence and etiology of elevated aminotransferase levels in the United States. 1280 14

We examined the association of serum alanine aminotransferase (ALT) with features of the metabolic syndrome and whether it predicted incident diabetes independently of routinely measured factors in 5,974 men in the West of Scotland Coronary Prevention Study. A total of 139 men developed new diabetes over 4.9 years of follow-up. ALT, but not aspartate aminotransferase, levels increased progressively with the increasing number of metabolic syndrome abnormalities from (means +/- SD) 20.9 +/- 7.6 units/l in those with none to 28.1 +/- 10.1 units/l in those with four or more (P < 0.001). In a univariate analysis, men with ALT in the top quartile (ALT >/=29 units/l) had an elevated risk for diabetes (hazard ratio 3.38 [95% CI 1.99-5.73]) versus those in the bottom quartile (<17 units/l). ALT remained a predictor with adjustment for age, BMI, triglycerides, HDL cholesterol, systolic blood pressure, glucose, and alcohol intake (2.04 [1.16-3.58] for the fourth versus first quartile). In stepwise regression, incorporating ALT and C-reactive protein (CRP) together with metabolic syndrome criteria, elevated ALT (>/=29 units/l), and CRP (>/=3 mg/l) predicted incident diabetes, but low HDL cholesterol and hypertension did not. Thus, elevated ALT levels within the "normal" range predict incident diabetes. The simplicity of ALT measurement and its availability in routine clinical practice suggest that this enzyme activity could be included in future diabetes prediction algorithms.
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PMID:Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study. 1550 65

Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome, although it is not known whether markers of NAFLD, including elevated concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALK), predict the development of metabolic syndrome. Our objective was to investigate the associations of elevated AST, ALT, and other liver markers, including C-reactive protein (CRP), with incident National Cholesterol Education Program-defined metabolic syndrome among 633 subjects in the Insulin Resistance Atherosclerosis Study who were free of metabolic syndrome at baseline. Insulin sensitivity (Si) and acute insulin response (AIR) were directly measured from the frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years. After 5.2 years, 127 individuals had developed metabolic syndrome. In separate logistic regression models adjusting for age, sex, ethnicity, clinic, and alcohol consumption, subjects in the upper quartiles of ALT, ALK, and CRP were at significantly increased risk of incident metabolic syndrome compared with those in the lowest quartile: ALT, odds ratio 2.50 (95% CI 1.38-4.51); ALK, 2.28 (1.24-4.20); and CRP, 1.33 (1.09-1.63). Subjects in the upper quartile of the AST-to-ALT ratio were at significantly reduced metabolic syndrome risk (0.40 [0.22-0.74]). After further adjustment for waist circumference, Si, AIR, and impaired glucose tolerance, the associations of ALT and the AST-to-ALT ratio with incident metabolic syndrome remained significant (ALT, 2.12 [1.10-4.09]; the AST-to-ALT ratio, 0.48 [0.25-0.95]). These associations were not modified by ethnicity or sex, and they remained significant after exclusion of former and heavy drinkers. In conclusion, NAFLD markers ALT and the AST-to-ALT ratio predict metabolic syndrome independently of potential confounding variables, including directly measured Si and AIR.
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PMID:Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. 1624 37

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 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

Increasing evidence suggests an association between elevated serum aminotransferase level and the metabolic syndrome. However, the significance of relatively low levels of aminotransferase in relation to the metabolic syndrome has not been fully investigated in the general population. We investigated the association between serum amiontransferase level and the metabolic syndrome using data from a nationwide survey in Korea. We measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and metabolic conditions among 9771 participants aged 20 or more in the 1998 and 2001 Korean National Health and Nutrition Examination Surveys. Metabolic syndrome was defined according to NCEP-ATP III criteria with a modified waist circumference cutoff (men > 90 cm; women > 80 cm). Serum aminotransferase level, even within normal range, was associated with the metabolic syndrome independent of age, body mass index, waist circumference, smoking, and alcohol intake. Compared with the lowest level (< 20 IU/L), the adjusted odds ratios (95% CI) for an AST level of 20-29, 30-39, 40-49 and > or = 50 IU/L were 1.10 (0.85-1.42), 1.37 (1.02-1.83), 1.62 (1.08-2.43), and 2.25 (1.47-3.44) in men, and 1.18 (0.99-1.41), 1.43 (1.29-1.83), 1.71 (1.09-2.68), and 2.14 (1.20-3.80) in women, respectively. Corresponding odds ratios for ALT levels were 1.27 (0.99-1.63), 1.69 (1.28-2.23), 2.17 (1.58-2.99), and 2.65 (1.96-3.58) in men, and 1.44 (1.22-1.70), 1.65 (1.26-2.15), 2.94 (1.93-4.47), and 2.25 (1.54-3.30) in women, respectively. In conclusion, elevated serum aminotransferase levels, even in the normal to near normal range, are associated with features of the metabolic syndrome.
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PMID:Normal serum aminotransferase levels and the metabolic syndrome: Korean National Health and Nutrition Examination Surveys. 1694 45

We compared the levels of hepatic enzymes in 220 Japanese men with metabolic syndrome with those in age and sex-matched subjects without the syndrome. Metabolic syndrome was defi ned by the new criteria published in Japan, and hepatic enzymes, i.e., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (gammaGTP), were measured. AST, ALT and gammaGTP in subjects with metabolic syndrome were significantly higher than those in subjects without the syndrome, and metabolic syndrome was closely associated with hepatic enzymes in this cohort of Japanese men.
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PMID:Comparison of hepatic enzymes between Japanese men with and without metabolic syndrome. 1733 39

Biochemical traits such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and uric acid are associated with obesity, and with risk of cardiovascular disease, metabolic syndrome and diabetes. Each is subject to genetic influences, but little is known about changes in genetic and environmental influences on these traits over time. We investigated the contribution of genetic and environmental influences to variation in these biochemical traits in adolescent twins and their nontwin siblings from 965 twin families. Twins were studied at ages 12, 14 and 16 years. Multivariate genetic models that included effects of age and sex were fitted to determine whether the same or different genetic or environmental factors influence each trait at different ages. Results showed that the genetic factors influencing AST, ALT, GGT and uric acid change over time during adolescence, and that the magnitude of these effects differs between males and females. The nonshared environment effects were generally time specific. There are developmental changes in genes affecting these traits during adolescence.
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PMID:A longitudinal genetic study of uric acid and liver enzymes in adolescent twins. 1790 17

Evidence suggesting an effect of fetal growth on liver development and function stems from both animal and human studies. The association of birthweight with adult markers of liver damage and function was examined in a random sample of 2101 British women aged 60-79 years. Age-adjusted natural logged levels of alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) decreased linearly across increasing thirds of birthweight. Alkaline phosphatase (ALP) levels were higher in women of the lowest third of the birthweight distribution compared with other women. No evidence was found for associations of birthweight with aspartate aminotransferase (AST), total bilirubin and albumin. After full adjustment for social class, physical activity, smoking and alcohol consumption, an increase in one standard deviation of birthweight (691 g) was associated with a 2% ([95% CI 0%, 4%], P = 0.021) decrease in the geometric mean of ALT, a 4% decrease in GGT ([95% CI 1%, 6%], P = 0.008) and a 2% decrease in ALP ([95% CI 0%, 3%], P = 0.001). Associations of birthweight with ALT and GGT, but not with ALP, were attenuated when adjusting for components of the metabolic syndrome. These findings suggest that factors affecting intrauterine growth may increase the propensity for adult liver damage. The attenuation of associations with adjustment for components of the metabolic syndrome is in line with non-alcoholic fatty liver disease, indicated by elevated ALT and GGT, being the hepatic manifestation of the metabolic syndrome, and of the influence of perinatal factors on this syndrome.
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PMID:The associations between birthweight and adult markers of liver damage and function. 1817 79


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