Abstract
BACKGROUND/AIMS: Alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are widely used markers of liver disease. Several population-based cohort studies have found associations of these liver enzymes with all-cause mortality. None of these studies controlled for genetic variation as well as fetal and early life exposure, whether environmental or genetic. METHODS: We studied the associations of ALT and GGT with all-cause mortality using data for 686 twins (73-94 years old) included in the Longitudinal Study of Aging Danish Twins. RESULTS: An increase in 1 logged U/L of GGT was associated with a 15% increase in the hazard ratio (HR) for mortality [95% confidence interval (CI) 0.99, 1.32] but there was no strong evidence of an association of ALT with all-cause mortality (HR=1.07, 95% CI 0.82, 1.40) when controlling for potential confounders. In this analysis, the study population was treated as individuals, with similarities between twins accounted for by using robust standard errors. However, an intrapair analysis in which the proportion of twin pairs in which the twin with the higher level of ALT or GGT died first was compared with 50% (expected under the null hypothesis), found no strong evidence that higher ALT or GGT was associated with earlier death within twin pairs; the results were consistent in both monozygotic and dizygotic twins. CONCLUSIONS: gamma-glutamyltransferase but not ALT predicts mortality among older Danish twins when using traditional methods for controlling for potential confounders and existing diabetes and cardiovascular disease. Environmental developmental origins may explain the association, but larger twin studies are required to replicate our findings.