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Gamma glutamyl transpeptidase (GTP) is a cell surface glycoprotein that cleaves glutathione, glutathione conjugates and other gamma-glutamyl compounds. The most intense expression of GTP activity is found on the surface of renal proximal tubule cells, hepatic bile canaliculi and capillary endothelial cells within the nervous system. Inhibition of GTP in the kidney causes glutathionuria, which results in a loss of amino acids from the body. The presence of GTP in extrarenal tissues may prevent loss of glutathione and its constituent amino acids from the body (Hanigan & Frierson 1996). Estimation of GTP levels is widely used in clinical practice as a biological marker of alcohol consumption as well as for diagnosing liver and biliary tract disease. However, within its normal range, GTP has other, even stronger determinants than alcohol consumption, such as BMI and total cholesterol. In the third Tromsø study, the alcohol variables explained about 20 and 10 percent of the total variance in males and females, respectively (Nilssen et al. 1990). Interestingly, GTP levels have been associated with all-cause mortality, largely due to a significant increase in deaths from ischemic heart disease and other non-cardiovascular disease causes, i.e., non-cancer deaths, in the top quintile of the GTP distribution (the British Regional Heart Study, Wannamethee et al. 1995).
A positive correlation between GTP and BP has been observed in surveys of alcohol consumption (Gyntelberg & Meyer 1974, Henningsen et al. 1980), and such a relationship has been particularly evident in established hypertensives (Henningsen et al. 1980). However, in subjects with normal or high-normal blood pressure levels, GTP accounted for only 4% of the BP variation (Henningsen et al. 1983).
The significant relationship between serum GTP and blood pressure in alcohol drinkers (Yamada et al. 1989) and in abstinent obese subjects (Yamada et al. 1990) suggests common mechanisms for the elevation of GTP and blood pressure. In a Cretan population with low cardiovascular mortality, hypertensives had higher GTP values even though they consumed less alcohol than normotensives (Koutis et al. 1992). The incidence of hypertension during 5-year follow-up has been shown to be higher in subjects with GTP levels above 50 units/l than in those with normal levels (Yamada et al. 1991). However, the significant relationship between GTP and blood pressure became nonsignificant after adjustment for plasma insulin, whereas plasma insulin remained to have a significant association with blood pressure (Ikai 1995). Furthermore, elevated serum GTP levels have been shown to predict the development of NIDDM in men independently of serum glucose, body mass index and other predictors of NIDDM (Perry et al. 1998).
Elevated levels of liver enzymes in obese subjects have been associated with hepatic steatosis, possibly due to excess insulin in the liver (Nomura et al. 1986, Wanless et al. 1989). Furthermore, hepatic steatosis is thought to cause hepatic insulin resistance and to contribute to the development of systemic insulin resistance and hyperinsulinemia in obese subjects (Kissebah 1991, Ikai et al. 1995).
No available studies have focused on the relationship between GTP and the metabolic syndrome in population-based cohorts.