title: Alanine aminotransferase, gamma-glutamyltransferase (GGT) and all-cause mortality: results from a population-based Danish twins study alanine aminotransferase, GGT and mortality in elderly twins.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Social Medicine, MRC Centre for Causal Analysis in Translational Epidemiology, University of Bristol, Bristol BS8 2BN, UK. abigail.fraser@bristol.ac.uk
authors.forename: Abigail
authors.initials: A
authors.lastname: Fraser
authors.forename: Mikael
authors.initials: M
authors.lastname: Thinggaard
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D002318:Cardiovascular Diseases / Q000401:mortality; D003920:Diabetes Mellitus / Q000401:mortality; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009026:Mortality; D016016:Proportional Hazards Models; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase
references.citation: Am J Gastroenterol. 2008 Sep;103(9):2263-71
references.pmid: 18684196
references.citation: Am J Epidemiol. 1995 Oct 1;142(7):699-708
references.pmid: 7572939
references.citation: Acta Med Okayama. 2007 Feb;61(1):31-4
references.pmid: 17332839
references.citation: Free Radic Res. 2004 Jun;38(6):535-9
references.pmid: 15346644
references.citation: Ugeskr Laeger. 2007 Jun 18;169(25):2398-403
references.pmid: 17594827
references.citation: Gastroenterology. 2009 Feb;136(2):477-85.e11
references.pmid: 19100265
references.citation: Nat Genet. 2008 Dec;40(12):1461-5
references.pmid: 18820647
references.citation: J Epidemiol. 2006 Jan;16(1):15-20
references.pmid: 16369104
references.citation: Am J Hum Genet. 2008 Oct;83(4):520-8
references.pmid: 18940312
references.citation: Diabetes Care. 2009 Apr;32(4):741-50
references.pmid: 19131466
references.citation: Prev Med. 1997 May-Jun;26(3):305-10
references.pmid: 9144754
references.citation: Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2729-35
references.pmid: 17932318
references.citation: Clin Chem. 2001 Jan;47(1):81-7
references.pmid: 11148181
references.citation: Twin Res Hum Genet. 2007 Apr;10(2):255-65
references.pmid: 17564515
references.citation: Diabetologia. 2008 Mar;51(3):402-7
references.pmid: 18071669
references.citation: Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):127-33
references.pmid: 17095717
references.citation: Int Arch Occup Environ Health. 1998 Sep;71(6):405-12
references.pmid: 9766914
references.citation: Diabetologia. 2004 Aug;47(8):1360-9
references.pmid: 15309287
references.citation: J Epidemiol Community Health. 2008 Jan;62(1):48-53
references.pmid: 18079333