The effect of liver enzymes on body composition: A Mendelian randomization study.
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Date
2020-02-11
Open Access Location
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS
Rights
(c) 2020 The Author/s
CC BY 4.0
CC BY 4.0
Abstract
Background
Higher alanine transaminase (ALT), indicating poor liver function, is positively associated with diabetes but inversely associated with body mass index (BMI) in Mendelian randomization (MR) studies, suggesting liver function affects muscle mass. To clarify, we assessed the associations of liver enzymes with muscle and fat mass observationally with two-sample MR as a validation.
Methods
In the population-representative “Children of 1997” birth cohort (n = 3,455), we used multivariable linear regression to assess the adjusted associations of ALT and alkaline phosphatase (ALP) at ~17.5 years with muscle mass and body fat percentage observationally. Genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) were applied to fat-free and fat mass in the UK Biobank (n = ~331,000) to obtain unconfounded MR estimates.
Results
Observationally, ALT was positively associated with muscle mass (0.11 kg per IU/L, 95% confidence interval (CI) 0.10 to 0.12) and fat percentage (0.15% per IU/L, 95% CI 0.13 to 0.17). ALP was inversely associated with muscle mass (-0.03 kg per IU/L, 95% CI -0.04 to -0.02) and fat percentage (-0.02% per IU/L, 95% CI -0.03 to -0.01). Using MR, ALT was inversely associated with fat-free mass (-0.41 kg per 100% in concentration, 95% CI -0.64 to -0.19) and fat mass (-0.58 kg per 100% in concentration, 95% CI -0.85 to -0.30). ALP and GGT were unclearly associated with fat-free mass or fat mass.
Conclusion
ALT reducing fat-free mass provides a possible pathway for the positive association of ALT with diabetes and suggests a potential target of intervention.ovides a possible pathway for the positive association of ALT with diabetes and suggests a potential target of intervention.
Description
Keywords
Adolescent, Alanine Transaminase, Alkaline Phosphatase, Body Composition, Body Mass Index, Cohort Studies, Female, Hand Strength, Humans, Linear Models, Liver, Male, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, gamma-Glutamyltransferase
Citation
Liu J, Au Yeung SL, Kwok MK, Leung JYY, Hui LL, Leung GM, Schooling CM. (2020). The effect of liver enzymes on body composition: A Mendelian randomization study.. PLoS One. 15. 2. (pp. e0228737-).