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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:587.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Elevated Gamma-Glutamyltransferase Activity and Perturbed Thiol Profile Are Associated With Features of Metabolic Syndrome

Philippe Giral; Nelly Jacob; Caroline Dourmap; Boris Hansel; Alain Carrié; Eric Bruckert; Xavier Girerd; M. John Chapman

From the Unités de Prévention Cardiovasculaire (P.G., C.D., B.H., E.B., X.G.), Service d’Endocrinologie-Métabolisme, Assistance Publique/Hopitaux de Paris, Groupe Hospitalier Pitié-Salpétrière–Université Pierre et Marie Curie; Laboratoire de Biochimie (N.J.), Assistance Publique/Hopitaux de Paris, Groupe Hospitalier Pitié-Salpétrière–Université Pierre et Marie Curie; Dyslipoproteinemia and Atherosclerosis Research Unit (P.G., B.H., A.C., E.B., X.G., M.J.C.), UMRS 551, National Institute for Health and Medical Research (INSERM) and Pierre et Marie Curie University (UPMC–Paris VI); Service de Biochimie Médicale (A.C.), Assistance Publique/Hopitaux de Paris, Groupe Hospitalier Pitié-Salpétrière–Université Pierre et Marie Curie, Paris, France.

Correspondence to Docteur P. Giral, Unités de Prévention Cardiovasculaire-Groupe Hospitalier Pitié-Salpêtrière, 47–83 boulevard de l’hôpital, 75651 Paris Cedex 13, France. E-mail philippe.giral{at}psl.aphp.fr

Abstract

Background— Prospective cohort studies have revealed that plasma -glutamyltransferase (GGT) activity exhibits a positive association with coronary artery disease. GGT which is equally elevated in metabolic syndrome (MS), is the major regulator of circulating concentrations of thiol compounds derived from glutathione (GSH) cleavage, ie, cysteine and cysteinyl glycine. We compared the circulating thiol profile in a cohort of patients displaying atherogenic dyslipidemia with and without MS.

Methods and Results— This cross-sectional study involved 1131 dyslipidemic patients in primary prevention of whom 26% presented with MS. GGT activity and plasma cysteinyl-glycine and cysteine concentrations were higher in MS patients; by contrast, levels of GSH were significantly lower (P<10 to 4 for all comparisons versus patients without MS). We compared patient groups on the basis of the number of MS criteria which were concomitantly present. A progressive decrease in glutathione levels in contrast to a progressive increase in both cysteinyl–glycine and cysteine levels, and GGT activity, was observed as a function of the number of MS components in the overall population (P for trend <10^–6).

Conclusion— Dyslipidemic patients exhibiting MS are characterized by elevated GGT activity which is associated with perturbed metabolism of thiol compounds.

We evaluated components of the plasma redox system in dyslipidemic patients with metabolic syndrome as a function of the number of qualifying criteria. Our findings suggest that metabolic syndrome is characterized by elevated GGT activity which is in turn associated with a cascade of abnormalities in the thiol redox system.

Key Words: metabolic syndrome • -glutamyltransferase • glutathione • cysteine • oxidation