Importance of gamma-glutamyl transferase elevation in patients with Fontan-associated liver disease.

AIM: In patients with Fontan-associated liver disease (FALD), gamma-glutamyl transferase (GGT) levels are often elevated, however, its clinical importance is unclear. We investigated the relationship between the clinical course of FALD and GGT levels. METHODS: We enrolled 145 patients with FALD who underwent right-heart catheterization (RHC) and visited our department. Ursodeoxycholic acid (UDCA) was administered to 62 of the patients. Patients with GGT levels <50 and ≥50 U/L were compared. Follow-up RHC was undertaken in 76 patients. Cases in which GGT levels decreased by ≥10% or <50 U/L were defined as improved (n = 33). RESULTS: Patients with GGT levels ≥50 U/L had significantly lower levels of albumin and higher levels of alanine transaminase (ALT) but no significant differences in RHC factors. Over a 4.6-year period, 43.4% showed improvement in GGT levels. Improved cases had significantly lower total bilirubin (1.1 vs. 1.6 mg/dL), AST (22 vs. 28 U/L), and ALT (18 vs. 27 U/L) levels than nonimproved cases (n = 29, p < 0.05), and the change in platelet count (-0.5 vs. -3.0 × 10-4/µL) was significantly lower in the latter (p = 0.03). The improvement rate was significantly higher in UDCA-treated cases (55.2%) with GGT levels ≥50 U/L compared to cases not treated with UDCA (18.2%, p = 0.04). CONCLUSION: In cases of FALD with no improvement in GGT level, the platelet count decreased over time, suggesting progression of fibrosis. Physicians should be aware of the importance of a high GGT level in patients with FALD.

The discovery of GGT1 as a novel gene for ischemic stroke conferring protection against disease risk in non-smokers and non-abusers of alcohol.

OBJECTIVES: Increased plasma gamma-glutamyl transferase (GGT1) has been identified as a robust and independent risk factor for ischemic stroke (IS), but the molecular mechanisms of the enzyme-disease association are unclear. The present study investigated whether polymorphisms in the GGT1 gene contribute to IS susceptibility. MATERIALS AND METHODS: DNA samples obtained from 1288 unrelated individuals (600 IS patients and 688 controls) were genotyped for common single nucleotide polymorphisms of GGT1 using the MassArray-4 platform. RESULTS: The rs5751909 polymorphism was significantly associated with decreased risk of ischemic stroke regardless sex and age (Pperm ≤ 0.01, dominant genetic model). The haplotype rs4820599A-rs5760489A-rs5751909A showed strong protection against ischemic stroke (OR 0.53, 95 %CI 0.36 - 0.77, Pperm ≤ 0.0001). The protective effect of SNP rs5751909 in the stroke phenotype was successfully replicated in the UK Biobank, SiGN, and ISGC cohorts (P ≤ 0.01). GGT1 polymorphisms showed joint (epistatic) effects on the risk of ischemic stroke, with some known IS-associated GWAS loci (e.g., rs4322086 and rs12646447) investigated in our population. In addition, SNP rs5751909 was found to be strongly associated with a decreased risk of ischemic stroke in non-smokers (OR 0.54 95 %CI 0.39-0.75, Pperm = 0.0002) and non-alcohol abusers (OR 0.43 95 %CI 0.30-0.61, Pperm = 2.0 × 10-6), whereas no protective effects of this SNP against disease risk were observed in smokers and alcohol abusers (Pperm < 0.05). CONCLUSIONS: We propose mechanisms underlying the observed associations between GGT1 polymorphisms and ischemic stroke risk. This pilot study is the first to demonstrate that GGT1 is a novel susceptibility gene for ischemic stroke and provides additional evidence of the genetic contribution to impaired redox homeostasis underlying disease pathogenesis.

Gamma-Glutamyl Transferase as a Diagnostic Marker of Metabolic Syndrome.

Introduction The metabolic syndrome consists of metabolic abnormalities that increase the risk of cardiovascular disease (CVD) and cerebrovascular disease. Metabolic syndrome (MetS) is a growing problem worldwide, and substantial efforts have been made in the last years to identify early, minimally invasive blood-based biomarkers for its diagnosis. This study attempted to assess how serum Gamma-Glutamyl Transferase (GGT) performed as an ideal endogenous substance for the diagnosis of metabolic syndrome and hence estimate cardiovascular risks. Methodology This study has been undertaken to assess the role of GGT as a marker in the diagnosis of metabolic syndrome and to assess the sensitivity and specificity of GGT in the diagnosis of metabolic syndrome. One hundred and eighty subjects were recruited comprising 90 cases of MetS and an equal number of age and gender-matched controls. Patients were recruited into the study group after satisfying the International Diabetes Federation (IDF) criteria for MetS. GGT values were obtained for both groups apart from other parameters. The patients in the study were also evaluated for the presence of cardiovascular diseases and cerebrovascular accidents (CVA). Results Sixty cases have GGT levels above the normal range (55 in males and 38 in females), and none in the control group have GGT levels above normal. This difference is statistically significant (p=0.01). The sensitivity was found to be 67% and 94% for males and females respectively. The specificity was found to be 100% and 98% for males and females respectively. Among the 90 cases, 20 (22.2%) patients developed cardiovascular disease. None in the control group developed cardiovascular disease. This difference is statistically significant (p<0.05). Conclusion Serum GGT appears to be an easily available and fairly good marker for diagnosing patients with metabolic syndrome and is independent of other parameters of metabolic syndrome. It is also a strong predictor of cardiovascular disease. Hence GGT can be considered a potential marker for the evaluation of patients with metabolic syndrome.

Ketamine uropathy: Clinical experience in a high prevalence center.

OBJECTIVES: Ketamine uropathy causes inflammatory changes to the urothelium, manifesting as significant lower urinary tract symptoms, small bladder capacity, and pelvic pain. Upper tract involvement and hydronephrosis can occur. Data from UK centers are limited, and no formal treatment guidelines exist. PATIENTS AND METHODS: All patients with ketamine uropathy presenting to our unit over an 11-year period were identified through operative and clinic lists, emergency presentations, and a prospectively collected local database. Demographic data, biochemical findings, imaging techniques, and both medical and surgical management were recorded. RESULTS: A total of 81 patients with ketamine uropathy were identified from 2011 to 2022; however, a large proportion presented from 2018 onwards. The average age at presentation was 26 years (interquartile range [IQR]: 27-34), 72.8% were male, and average follow-up time was 34 months (IQR: 8-46). Therapeutic interventions included anticholinergic medication, cystodistension, and intravesical sodium hyaluronate. Hydronephrosis was present in 20 (24.7%) patients and nephrostomy insertion was required in six. One patient underwent bladder augmentation surgery. Serum gamma-glutamyl transferase and length of follow-up were significantly higher in patients with hydronephrosis. Adherence to follow-up was poor. CONCLUSIONS: We present a large cohort of patients with ketamine uropathy from a small town in the UK which is unusual. The incidence appears to be rising, in-keeping with increasing recreational ketamine use and should be of concern to urologists. Abstinence is a key aspect of management, and a multi-disciplinary approach works best particularly as many patients are lost to follow-up. The development of formal guidance would be helpful.

Significance of Fib4 index as an indicator of alcoholic hepatotoxicity in health examinations among Japanese male workers: a cross-sectional and retrospectively longitudinal study.

BACKGROUND: Fib4 index (Fib4) is clinically used as a noninvasive marker of liver fibrosis. In this study, we aimed to preliminarily investigate whether Fib4 can be used to detect individuals who need assessment for alcoholic liver disease (ALD) in the general population by clarifying the detailed association of Fib4 with alcohol consumption and gamma-glutamyl transferase (GGT) among male workers. METHODS: We analyzed data sets on the comprehensive medical examinations of male workers as cross-sectional and retrospectively longitudinal studies. We enrolled 10 782 males (mean age: 52.2 ± 10.2 years) in FY2019 and 7845 males (mean follow-up: 12.6 ± 6.7 years) who could be consecutively followed up for 20 years from FY2000 to FY2019. Data were evaluated using logistic regression and COX proportional analysis. RESULTS: In the cross-sectional setting, the rate of Fib4 ≥ 2.67 in heavy drinkers (≥ 40 g of ethanol/day) was increased dose dependently in those over 65 years old, and that of body mass index ≥ 30 kg/m2 was increased in those over 60 years old, but not in those with fatty liver. The odds ratio (OR) (95% confidence interval [CI]) for heavy drinking was 4.30 (95% CI = 1.90-9.72), and GGT ≥ 200 IU/L was considerably high (OR = 29.05 [95% CI = 17.03-49.56]). In the longitudinal setting, heavy drinkers and those with GGT ≥ 200 IU/L at 10 years after the baseline showed an increased risk for Fib4 ≥ 2.67 (hazard ratio = 2.17 [95% CI = 1.58-2.98] and 7.65 [95% CI 5.26-11.12], respectively). CONCLUSIONS: The development of Fib4 ≥ 2.67 after 10 years was associated with heavy alcohol drinking and GGT level ≥ 200 IU/L. Therefore, Fib4 combined with GGT could indicate high risk of ALD. However, clinical examinations and course observations are essentially needed.

The Mystery of Episodic Recurrent Jaundice in a Young Male: Cholestasis With a Normal Gamma-Glutamyl Transferase.

Benign recurrent intrahepatic cholestasis (BRIC) is a very rare autosomal recessive genetic disorder which presents with recurrent jaundice. We report the case of a young male with a history of methamphetamine use who presented with recurrent episodes of right upper quadrant abdominal pain, vomiting, dark urine, and pale stools. These symptoms always resolved within four weeks of presentation. During these episodes, the patient had a cholestatic pattern derangement of liver function tests with a normal gamma-glutamyl transferase (GGT). Workup for abnormal transaminases was unremarkable. A percutaneous liver biopsy obtained on the third visit was notable for a parenchymal lobule that exhibited slight Kupffer cell hyperplasia and subtle evidence of canalicular cholestasis. There was no evidence of cirrhosis, steatosis, hepatitis, or malignancy. Thus, a diagnosis of BRIC was made, and the patient was managed conservatively. Recognition of this rare entity is critical since its benign natural history is reassuring for the patient, and physicians can refrain from repetitive expansive and costly workups.

Stratification of population in NHANES 2009-2014 based on exposure pattern of lead, cadmium, mercury, and arsenic and their association with cardiovascular, renal and respiratory outcomes.

BACKGROUND: Environmental exposure to toxic metals is an important risk factor to human health. Traditional methods have examined associations between a health endpoint and exposure to heavy metals by either univariate or multiple regression. In the setting of ubiquitous heterogeneous environmental exposures, statistical methods that incorporate mixed exposures are increasingly relevant and may provide new insight into the association between metal exposure and important cardiovascular, renal and respiratory outcomes. OBJECTIVE: The objective of this study was to classify the population of National Health and Nutrition Examination Survey (NHANES) into different exposure subgroups using modern unsupervised clustering methods based on lead, cadmium, mercury, and arsenic measured in urine or whole blood, and to assess the association between the identified exposure groups and twelve important health endpoints. METHODS: We analyzed a sub-cohort of 9662 subjects participating in the 6 cycles (2003-2004 to 2013-2014) of NHANES study. The urine levels of 3 heavy metals (total arsenic, lead, cadmium) and blood levels of 3 heavy metals (lead, cadmium and mercury) were analyzed using a two-step approach. In the first step, we stratified the population into subgroups using unsupervised clustering (k-medoids) based on levels of metals either in urine or in blood. Then, we examine the association between 12 health endpoints and identified exposure subgroups while controlling for age, sex, race/ethnicity, education, smoking status, BMI, and urinary creatinine. RESULTS: The k-medoids algorithm clustered NHANES population into 2 groups based on either blood or urinary levels of heavy metals. The concentrations of all the three heavy metals were significantly different between the identified groups in blood (p < 2.2e-16) or in urine (p = 0). The group with higher concentrations was defined as the "high-exposure" group, while the group with lower concentrations was defined as "low-exposure" group. Association analysis with health outcomes suggested that the high-exposure group according to either blood or urinary metal levels had significantly higher total mortality (1.63-1.64 times higher, p < 0.0001), mortality caused by malignant neoplasms (2.05-2.62 times higher, p < 0.0002), Gamma-glutamyl transferase (GGT) (1.03-1.05 times higher, p < 0.0001). In addition, the high-exposure group based on blood levels was also significantly associated with SBP, death related to hypertension, heart disease and chronic lower respiratory disease, while the high-exposure group based on urinary concentrations had higher mortality related to nephritis. CONCLUSIONS: We proposed an unsupervised clustering method to stratify the population into high- and low-exposure groups based on the co-exposure of heavy metals. The high-exposure groups, characterized by higher metal concentrations, had significant higher GGT, SBP, DBP, and mortality rates suggesting the detrimental effects of exposure to these heavy metals. The stratification of the NHANES population based on exposure patterns provides an informative method to study the impact of metal exposures on health outcomes.

Golgi protein 73, hepatocellular carcinoma and other types of cancers.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a low survival rate. The identification of mechanisms underlying the development of HCC helps uncover cellular and molecular targets for the diagnosis, prevention, and treatment of HCC. Golgi protein 73 (GP73) level is upregulated in HCC patients and potentially can be a therapeutic target. Despite many studies devoted to GP73 as a marker for HCC early diagnosis, there is little discussion about the function of GP73 in HCC tumorigenesis. Given the poor response to currently available HCC therapies, a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC. The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis. Its roles in other types of cancer are also discussed.

Pipe-3D: A Pipeline Based on Immunofluorescence, 3D Confocal Imaging, Reconstructions, and Morphometry for Biliary Network Analysis in Cholestasis.

Cholestasis, the impairment of bile flux out of the liver, is a common complication of many pathological liver disorders, such as cholangiopathies, primary biliary sclerosis, and primary biliary cirrhosis. Besides accumulation of bile acids in the liver and blood, it leads to a proliferative response of the biliary tree termed as a ductular reaction. The ductular reaction is characterized by enhanced proliferation of cholangiocytes, which form the epithelial lining of bile ducts. This strong reaction of the biliary tree has been reported to generate a source of progenitor cells that can differentiate to hepatocytes or cholangiocytes during regeneration. On the other hand, it can cause periportal fibrosis eventually progressing to cirrhosis and death. In 2D histology, this leads to the appearance of an increased number of duct lumina per area of tissue. Yet, the biliary tree is a 3D vstructure and the appearance of lumina in thin slices may be explained by the appearance of novel ducts or by ramification or convolution of existing ducts in 3D. In many such aspects, traditional 2D histology on thin slices limits our understanding of the response of the biliary tree. A comprehensive understanding of architecture remodeling of the biliary network in cholestasis depends on robust 3D sample preparation and analysis methods. To that end, we describe pipe-3D, a processing and analysis pipeline visualization based on immunofluorescence, confocal imaging, surface reconstructions, and automated morphometry of the biliary network in 3D at subcellular resolution. This pipeline has been used to discover extensive remodeling of interlobular bile ducts in cholestasis, wherein elongation, branching, and looping create a dense ductular mesh around the portal vein branch. Surface reconstructions generated by Pipe-3D from confocal data also show an approximately fivefold enhancement of the luminal duct surface through corrugation of the epithelial lamina, which may increase bile reabsorption and alleviate cholestasis. The response of interlobular ducts in cholestasis was shown to be in sharp contrast to that of large bile ducts, de novo duct formation during embryogenesis. It is also distinct from ductular response in other models of hepatic injury such as choline-deficient, ethionine-supplemented diet, where parenchymal tissue invasion by ducts and their branches is observed. Pipe-3D is applicable to any model of liver injury, and optionally integrates tissue clearing techniques for 3D analysis of thick (>500 µm) tissue sections.

Higher level of GGT during mid-pregnancy is associated with increased risk of gestational diabetes mellitus.

OBJECTIVE: This study was to explore the link between gamma-glutamyl transferase (GGT), alanine transaminase (ALT) and aspartate transaminase (AST) levels during early-middle pregnancy and subsequent risk of gestational diabetes mellitus (GDM). METHODS: In a prospective cohort study, pregnant women enrolled prior to 16 weeks of gestation were followed up until delivery. GGT, AST and ALT levels were tested during weeks 14-18 of gestation and oral glucose tolerance test was conducted during 24-28 weeks to screen GDM. RESULTS: The GDM rate was 8.1% (122/1512). Mean GGT level was higher in GDM than non-GDM women (18.7 ± 13.0 vs 14.5 ± 7.0, P < .001). The higher GGT level was 26.9~74.0 U/L, which was significantly associated with increased risk of GDM. The adjusted RR (95% CI) comparing higher GGT level versus lower was 5.40 (3.36-8.68). No significant correlation was found between ALT or AST levels and the risk of GDM. CONCLUSIONS: The results suggest that pregnant women with higher serum GGT during early-middle pregnancy have higher risk of developing GDM. A GGT level >26.9 U/L may indicate an increased risk of developing GDM later and should be further concerned.

Neurological Complications in a Polynesian Traveler with Dengue.

In recent times, there has been an increased focus on mosquito-borne Flaviviruses, in particular dengue and Zika. With the reappearance of dengue in Hawai'i and the mainland United States (US), clinicians should be aware of both the common presentations of dengue, as well as other less common complications associated with the disease. Dengue can result in neurologic disorders such as encephalopathy, encephalitis, immune-mediated syndromes, neuromuscular dysfunction, and neuro-ophthalmologic disorders. We present an interesting case of dengue that initially presented with classic symptoms (arthropathy, biphasic fever, and rash) and subsequently developed into a neurologic movement disorder with muscle tightening and twitching of the face, chest, and extremities. We review and update the epidemiology, biology, the clinical presentations including the neurologic complications associated with dengue, as well as their management and areas of future study in this field.

Augmented expression of gamma-glutamyl transferase 5 (GGT5) impairs testicular steroidogenesis by deregulating local oxidative stress.

An increasingly pro-oxidant environment has been widely implicated in causing dysfunction of testicular steroidogenesis, but little progress has been made in understanding the underlying molecular mechanism. Here, we report that gamma-glutamyl transferase 5 (GGT5), a key metabolism component responsible for the catalysis of important anti-oxidant glutathione (GSH), is predominantly expressed in mammalian Leydig cells (LCs). Deregulated GGT5 expression negatively correlates with testosterone deficiency in the testes of type 2 diabetic mice. Consistently, overexpression of GGT5 potentiates the susceptibility of TM3 LCs to spontaneous oxidative stress during luteinizing hormone (LH)-stimulated steroidogenesis. From a mechanistic standpoint, the deleterious effect of GGT5 overexpression on testicular steroidogenesis may stem from an alteration of the local redox state because of GSH deficiency. The above-mentioned response might involve the impairment of extracellular signal-related kinase activation mediated directly by oxidative injury or indirectly by abnormal P38 activation, which in turn inhibits steroidogenic acute regulatory protein abundance in mitochondria and thus significantly sabotages the rate-limiting step during LH-induced steroidogenesis. Alternatively, GGT5 overexpression induces heme oxygenase 1 (HO-1) expression, which, as a key catalyst responsible for the oxidative degradation of heme, may inhibit the activities of the cytochrome P450 monooxygenases, thus substantially impairing testicular steroidogenesis. These results, coupled with the differential roles of mitogen-activated protein kinases and HO-1 signaling in spermatogenesis, lead us to propose a model in which a delicate balance between these two pathways modulated by the GGT5/oxidative stress cascade plays a central role during LH-stimulated steroidogenesis.

Gamma-glutamyl transferase and cardiovascular disease.

Gamma-glutamyl transferase (GGT) is an enzyme located on the external surface of cellular membranes. GGT contributes in maintaining the physiological concentrations of cytoplasmic glutathione and cellular defense against oxidative stress via cleavage of extracellular glutathione and increased availability of amino acids for its intracellular synthesis. Increased GGT activity is a marker of antioxidant inadequacy and increased oxidative stress. Ample evidence suggests that elevated GGT activity is associated with increased risk of cardiovascular disease (CVD) such as coronary heart disease (CHD), stroke, arterial hypertension, heart failure, cardiac arrhythmias and all-cause and CVD-related mortality. The evidence is weaker for an association between elevated GGT activity and acute ischemic events and myocardial infarction. The risk for CVD or CVD-related mortality mediated by GGT may be explained by the close correlation of GGT with conventional CVD risk factors and various comorbidities, particularly non-alcoholic fatty liver disease, alcohol consumption, oxidative stress, metabolic syndrome, insulin resistance and systemic inflammation. The finding of GGT activity in atherosclerotic plaques and correlation of intra-plaque GGT activity with histological indexes of plaque instability may suggest a participation of GGT in the pathophysiology of CVD, particularly atherosclerosis. However, whether GGT has a direct role in the pathophysiology of CVD or it is an epiphenomenon of coexisting CVD risk factors or comorbidities remains unknown and Hill's criteria of causality relationship between GGT and CVD are not fulfilled. The exploration whether GGT provides prognostic information on top of the information provided by known cardiovascular risk factors regarding the CVD or CVD-related outcome and exploration of molecular mechanisms of GGT involvement in the pathophysiology of CVD and eventual use of interventions to reduce circulating GGT activity remain a duty of future studies.

Gamma glutamyl transferase is an independent determinant for the association of insulin resistance with nonalcoholic fatty liver disease in Bangladeshi adults: Association of GGT and HOMA-IR with NAFLD.

AIMS: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with insulin resistance (HOMA-IR) syndrome. Recently serum gamma glutamyl transferase (GGT) has been considered as surrogate marker of NAFLD leading to oxidative stress and hepatocellular damage. In the present study we examined the association of serum GGT and HOMA-IR with NAFLD in Bangladeshi adult subjects. MATERIALS AND METHODS: Under a cross-sectional analytical design a total of 110 subjects were recruited who came for their routine health check up in the BIHS Hospital, Darussalam, Dhaka, Bangladesh. After whole abdomen ultrasonography, 62 were diagnosed as non-NAFLD and 48 were NAFLD subjects. Serum glucose was measured by glucose-oxidase method, lipid profile and liver enzymes by enzymatic colorimetric method, glycosylated hemoglobin (HbA1c) was measured by high performance liquid chromatography (HPLC), serum insulin were measured by enzyme-linked immunosorbent assay. HOMA-IR was calculated by homeostasis model assessment (HOMA). RESULTS: NAFLD subjects had significantly higher levels of GGT and HOMA-IR as compared to their non-NAFLD counterparts. Multiple linear regression analysis showed a significant positive association of HOMA-IR with GGT after adjusting the effects of waist circumference (WC) and HbA1c. In binary logistic regression analysis, HOMA-IR and GGT were found to be significant determinants of NAFLD after adjusting the effects of WC and HbA1c. CONCLUSION: These results suggest that elevated levels of GGT and insulin resistance are more likely to develop NAFLD and thus support a role of these determinants in the pathogenesis of NAFLD in Bangladeshi adult subjects.

Urinary polycyclic aromatic hydrocarbons and measures of oxidative stress, inflammation and renal function in adolescents: NHANES 2003-2008.

OBJECTIVE: Recent evidence has suggested that polycyclic aromatic hydrocarbons (PAHs) may contribute to cardiometabolic and kidney dysfunction by increasing oxidative stress, but little is known about impacts in childhood. STUDY DESIGN: We performed cross-sectional analyses of 660 adolescents aged 12-19 years in the 2003-2008 National Health and Nutrition Examination Survey (NHANES), using levels of 10 monohydroxylated urinary PAH metabolites as our exposure. Our primary outcomes of interest were biomarkers of oxidative stress and renal function, including estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (ACR), insulin resistance, and serum uric acid, gamma glutamyl transferase (GGT) and C-reactive protein (CRP). RESULTS: We observed statistically significant associations between PAH metabolites and levels of serum GGT, CRP, uric acid and eGFR. Each 100% increase in 2-hydroxyphenanthrene was related to a 3.36% increase in uric acid (95% CI: 0.338-6.372; p=0.032), a 3.86% increase in GGT (95% CI: 1.361-6.362; p=0.005) and a 16.78% increase in CRP (95% CI: 1.848-31.689; p=0.029). Each 100% increase in 4-hydroxyphenanthrene was associated with a 6.18% increase in GGT (95% CI: 4.064-8.301; p<0.001) and a 13.66% increase in CRP (95% CI: 2.764-24.564; p=0.017). Each 100% increase in 9-hydroxyfluorene was associated with a 2.58% increase in GGT (95% CI: 0.389-4776; p=0.024). Each 100% increase in 3-hydroxyphenanthrene was associated with a 2.66% decrease in eGFR (95% CI: -4.979 to -0.331; p=0.028). CONCLUSIONS: Urinary PAH metabolites were associated with serum uric acid, GGT and CRP, suggesting possible impacts on cardiometabolic and kidney function in adolescents. Prospective work is needed to investigate the potential long-term health consequences of these findings.

The association of alcohol intake with γ-glutamyl transferase (GGT) levels: evidence for correlated genetic effects.

BACKGROUND: Blood levels of gamma-glutamyl transferase (GGT) are used as a marker for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT. However, there is variability in the response of GGT to alcohol use, which may result from genetic differences between individuals. This study aimed to determine whether the epidemiological association between alcohol intake and GGT at the population level is necessarily a causal one or may also reflect effects of genetic pleiotropy (genes influencing multiple traits). METHODS: Data on alcohol intake (grams alcohol/day) and GGT, originating from twins, their siblings and parents (N=6465) were analyzed with structural equation models. Bivariate genetic models tested whether genetic and environmental factors influencing alcohol intake and GGT correlated significantly. Significant genetic and environmental correlations are consistent with a causal model. If only the genetic correlation is significant, this is evidence for genetic pleiotropy. RESULTS: Phenotypic correlations between alcohol intake and GGT were significant in men (r=.17) and women (r=.09). The genetic factors underlying alcohol intake correlated significantly with those for GGT, whereas the environmental factors were weakly correlated (explaining 4-7% vs. 1-2% of the variance in GGT respectively). CONCLUSIONS: In this healthy population sample, the epidemiological association of alcohol intake with GGT is at least partly explained by genetic pleiotropy. Future longitudinal twin studies should determine whether a causal mechanism underlying this association might be confined to heavy drinking populations.

Evaluation of the oxidative stress in chronic alcoholics.

AIM: The present study was conducted to assess the activity of Gamma Glutamyl Transferase (GGT) and its association with oxidative stress in alcoholics. METHOD: Sixty male alcoholics with a history of alcohol abuse for more than five years were the subjects of this study. Twenty healthy male volunteers who matched in age and the socio-economic status, served as the control subjects. RESULTS: GGT, reduced glutathione (GSH, a key intra-cellular antioxidant) and malondialdehyde (MDA, a marker of the oxidative stress) were assayed in the plasma of the two groups, and the results were statistically analyzed. The activity of the plasma GGT, known as a marker of Alcoholic Liver Disease (ALD); was significantly higher in the alcoholics as compared to that in the healthy controls. CONCLUSION: There was a significant positive correlation between the enzyme activity and the plasma levels of MDA and this indicated that there was an increased release of this enzyme with enhanced oxidative damage, due to the generation of oxygen free radicals in the study group. There was a significantly increased level of MDA and a decrease in the level of GSH in the alcoholics as compared to those in the controls. Significant negative correlations between GGT and GSH, and between MDA and GSH were observed. The present study demonstrates that alcoholics have a compromised antioxidant defense system.

Diagnostic usefulness of serum gamma-glutamyl transferase ( GGT ) activity in fatty liver and relationship with other factors / 대한내과학회지

BACKGROUND: Gamma-glutamyl transferase(GGT) has found wide application as a diagnostic test in hepatobiliary disease, and has been used as the best single marker of alcohol intake. In spite of the wide use of GGT in clinical practice, knowledge concerning the distribution and the determinants of this risk factor in the normal population is spared in Korea. We tried to obtain a better evaluation of specificity of serum GGT by analysis of a large population of health examination. METHODS: GGT was measured in 17,140 males aged 17-86 years and 12,125 females aged 18-90 years screened in a health survey program. RESULTS: In multiple regression analyses, serum GGT level showed strong positive association with fatty liver, body mass index, serum levels of AST, ALT triglyceride, uric acid, alkaline phosphatase, systolic blood pressure, and diastolic blood pressure, and weakly positive association with serum levels of creatinine, total cholesterol, and fasting blood sugar. In females, menopause were positively associated with GGT. CONCLUSIONS: An elevated serum GGT levels is a strong indicator of hepatobiliary dysfunction or fatty liver. However, proper interpretation of a serum GGT elevation should be carefully considered in correlation with clinical data and laboratory findings.