4.8 Article

Genetic factors contribute to variation in serum alanine aminotransferase activity independent of obesity and alcohol: A study in monozygotic and dizygotic twins

Journal

JOURNAL OF HEPATOLOGY
Volume 50, Issue 5, Pages 1035-1042

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2008.12.025

Keywords

Heritability; ALT; Insulin; Liver fat; NAFLD; Twins

Funding

  1. European Commission [LSHM-CT-2005-018734]
  2. Academy of Finland [100499, 205585, 118555]
  3. Biovitrum Foundation
  4. Sigrid Juselius Foundation
  5. Liv och Halsa Foundation
  6. Helsinki University Central Hospital
  7. Research Foundation of the Orion Corporation
  8. Jalmari and Rauha Ahokas Foundation
  9. Juho Vainio Foundation
  10. Yrjo Jahnsson Foundation
  11. National Institute of Alcohol Abuse and Alcoholism
  12. Academy of Finland Centre of Excellence in Complex Disease Genetics
  13. Academy of Finland (AKA) [118555, 118555] Funding Source: Academy of Finland (AKA)

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Background/Aims: This study aimed to determine the heritability of serum alanine aminotransferase (S-ALT) and fasting serum insulin (fS-insulin) concentration as well as determine the association of these measures with liver fat content in young adult monozygotic (MZ) and dizygotic (DZ) twins. Methods: Three hundred and thirteen individual twins were recruited from a population-based cohort (n = 4929). The study subjects represented a wide range of body mass indexes (BMI), were free of any diseases or regular medications and had an intake of less than two drinks of alcohol/day. To verify that S-ALT is a marker of liver fat, it was measured by proton magnetic resonance spectroscopy ((1)H MRS) in 66 subjects. Heritability estimations were performed using BMI-and gender-adjusted values. Results: Intro-pair correlations were significantly higher in the MZ twins than the DZ twins for both S-ALT (0.65 for MZ and 0.04 for DZ) and tS-insulin (0.58 and 0.34, respectively). Heritability of S-ALT was 55%, and that of IS-insulin 61%. In the 66 subjects S-ALT (r = 0.70 for women and r = 0.50 for men, p <= 0.01 for both) and fS-insulin (r = 0.58 and r = 0.59, respectively, p <= 0.01 for both) concentrations correlated significantly with liver fat content. Conclusions: These twin data suggest that approximately 60%, of the variation in S-ALT, a marker of liver fat content, is genetically determined. (c) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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