Elevated gamma-glutamyltransferase activity and perturbed thiol profile are associated with features of metabolic syndrome

Background-Prospective cohort studies have revealed that plasma gamma-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.