High-sensitivity gamma-glutamyltransferase fraction pattern in alcohol addicts and abstainers

Franzini, Maria; Fornaciari, Irene; Vico, Tiziana; Moncini, M.; Cellesi, Valerio; Meini, Milo; Emdin, Michele; Paolicchi, Aldo

doi:10.1016/j.drugalcdep.2012.06.004

Cited by 21 publications

(25 citation statements)

References 11 publications

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“…Methods for measuring subfractions of total GGT activity (i.e., s-GGT, m-GGT, b-GGT and f-GGT) have been reported by Franzini et al [24], and disease-specific patterns of GGT subfractions and ratios of subtypes are emerging, for example, increased b-GGT has recently been associated with cardiovascular risk [27], whereas s-GGT was increased in alcoholics [39]. Our research is limited by not having this GGT subfraction data, which should be applied in future studies to better differentiate subgroups within larger cohorts by disease status, including those with isolated hepatic disease and those with multiorgan disease, that is, concomitant nonalcoholic fatty liver disease, metabolic disease and cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the potential to improve upon our methods by subfractionating GGT, the associations demonstrated here with total serum GGT activity remain valid. Other studies have demonstrated that participants with increased total serum GGT activity have increased GGT subfractions more associated with disease (i.e., non-f-GGT fractions), total serum GGT activity increased with increases in each subfraction (i.e., except f-GGT) and total serum GGT activity remains the most accessible biomarker to clinicians [26,27,39]. …”

Section: Discussionmentioning

confidence: 99%

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Associations Between Total Serum Ggt Activity and Metabolic Risk: MESA

Bradley

Fitzpatrick

Jenny³

et al. 2013

Biomarkers Med.

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Aim To evaluate associations between total serum GGT activity, metabolic risk factors and prevalent metabolic disease in MESA. Patients & methods Continuous associations between GGT and fasting blood glucose (FBG), fasting insulin, HbA1c and Homeostasis Model Assessment Index of Insulin Resistance (HOMA–IR) were evaluated in the entire MESA cohort and in metabolic disease subgroups using linear regression models incrementally adjusted for age, gender, site, race, lifestyle, traditional risk factors and medications. Cross-sectional odds of prevalent impaired FBG, metabolic syndrome and Type 2 diabetes were calculated for GGT quintiles in the entire cohort and in subgroups defined by age (< or ≥65 years) and ethnicity. Results In multivariable models, significant associations were present between GGT activity and FBG, fasting insulin, HbA1c and HOMA–IR, with the interaction between GGT and BMI affecting the association between GGT and HOMA–IR as well as the association between BMI and HOMA–IR (p < 0.0001). Adjusted odds ratios (95% CIs) of prevalent impaired FBG, metabolic syndrome and Type 2 diabetes for quintile 5 versus 1 in the entire cohort were 2.4 (1.7–3.5), 3.3 (2.5–4.5) and 2.8 (1.8–4.4), respectively (p < 0.0001). GGT associations weakened with age. The significance of linear trends for increased prevalent metabolic disease by increasing GGT quintile varied by ethnicity. Conclusion GGT is strongly associated with both cardiovascular and metabolic risk factors, including prevalent metabolic disease, in the MESA cohort.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Associations Between Total Serum Ggt Activity and Metabolic Risk: MESA

Bradley

Fitzpatrick

Jenny³

et al. 2013

Biomarkers Med.

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“…Metabolic and cardiovascular risk markers are important correlates of GGT fractions, in particular of b-GGT in healthy subjects [42] and in Framingham population [43]. It is noteworthy that non-alcoholic fatty liver disease, a component of the metabolic syndrome which is associated to increased cardiovascular risk [44], seems to be a rather specific cause of plasma b-GGT increase in blood [45], while alcohol abuse and liver diseases are more specifically associated with s-GGT elevation [46].…”

Section: Intra-plaque B-ggtmentioning

confidence: 99%

b-Gamma-glutamyltransferase activity in human vulnerable carotid plaques

Pucci¹,

Franzini

Matteucci

et al. 2014

Atherosclerosis

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a b s t r a c tObjective: The atherosclerotic plaque that is vulnerable to rupture and to superimposed thrombosis is mainly represented by a thin-cap fibroatheroma with or without ulceration/thrombosis and inflammatory infiltrates. Total serum gamma-glutamyltransferase (GGT) activity is an independent predictor for cardiovascular events. Four GGT fractions have been identified in plasma and only one of them (b-GGT) in atherosclerotic plaques, but the possible role of GGT in plaque pathophysiology has not been assessed yet. We investigated the relationships between plaque b-GGT activity and the histological features of plaque vulnerability. Methods and results: Plaque GGT activity was investigated in 65 patients undergoing carotid endarterectomy; plaques were histologically characterized and immunostained for GGT. Intra-plaque total and fractional GGT activity was determined by a cost-effective test of molecular size exclusion chromatography, and compared with histological markers of plaque vulnerability. Plaque cholesterol content was also measured by chromatography. b-GGT was the only fraction detected within the atherosclerotic plaques and intra-plaque b-GGT activity correlated to plaque cholesterol content (r ¼ 0.667, P < 0.0001), plasma b-GGT and f-GGT fractions (r ¼ 0.249; r ¼ 0.298, both P < 0.05). Higher b-GGT activity was found in thin-cap fibroatheromas and it was associated to histological markers of vulnerable plaques, i.e., larger necrotic areas, greater macrophage infiltration and higher cholesterol content (P < 0.05). Conclusions: intra-plaque b-GGT activity correlates with the histological markers of vulnerable plaque and with plasma b-GGT in human carotid atherosclerosis; these data support the possible role of b-GGT in clinically significant atherosclerotic disease.

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“…While f-GGT is the major circulating GGT fraction in healthy subjects in both sexes, in the pathological conditions examined so far, b-GGT and s-GGT accounted for most of total GGT increase [26-27]. Chronic viral hepatitis C [26] and alcoholic-liver disease [27] are characterized by the increase in s-GGT and the decrease in the b-GGT/s-GGT (b/s) ratio.…”

Section: Introductionmentioning

confidence: 99%

Correlates and reference limits of plasma gamma-glutamyltransferase fractions from the Framingham Heart Study

Franzini

Fornaciari

Rong

et al. 2013

Clinica Chimica Acta

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Background We assessed GGT fractions correlates and their reference values in the Offspring Cohort of the Framingham Heart Study. Methods Correlates of GGT fractions were assessed by multivariable regression analysis in 3203 individuals [47% men, mean age (SD): 59 (10) yrs.]. GGT fractions reference values were established by empirical quantile analysis in a reference group of 432 healthy subjects [45% men, 57 (10) years]. Results Fractional GGT levels were higher in men than in women (P < 0.0001). In both sexes, fractions were associated with: triglycerides were associated with b-GGT, alcohol consumption with m-, s- and f-GGT. C-reactive protein with m- and s-GGT, while plasminogen activator inhibitor-1 with b- and f-GGT. Body mass index, blood pressure, glucose and triglycerides correlated with b- and f-GGT. In comparison with the reference group [b-GGT/s-GGT median (Q1-Q3): 0.51 (0.35-0.79) U/L], subjects affected by cardiovascular disease or diabetes showed no change of b/s ratio [0.52 (0.34-0.79) U/L, 0.57 (0.40-0.83) U/L, respectively]. The b/s ratio was higher in presence of metabolic syndrome [0.61 (0.42-0.87) U/L, P<0.0001], while lower in heavy alcohol consumers [0.41 (0.28-0.64) U/L, P<0.0001]. Conclusions Metabolic and cardiovascular risk markers are important correlates of GGT fractions, in particular of b-GGT.

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High-sensitivity gamma-glutamyltransferase fraction pattern in alcohol addicts and abstainers

Cited by 21 publications

References 11 publications

Associations Between Total Serum Ggt Activity and Metabolic Risk: MESA

Associations Between Total Serum Ggt Activity and Metabolic Risk: MESA

b-Gamma-glutamyltransferase activity in human vulnerable carotid plaques

Correlates and reference limits of plasma gamma-glutamyltransferase fractions from the Framingham Heart Study

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