The effect of liver enzymes on body composition: A Mendelian randomization study

• Published in: PloS one 2020-02, Vol.15 (2), p.e0228737-e0228737
• Main Authors: Liu, Junxi, Au Yeung, Shiu Lun, Kwok, Man Ki, Leung, June Yue Yan, Hui, Lai Ling, Leung, Gabriel Matthew, Schooling, C Mary
• Format: Article
• Language: English
• Subjects: Adolescent; Age; Alanine; Alanine transaminase; Alanine Transaminase - genetics; Alanine Transaminase - metabolism; Alkaline phosphatase; Alkaline Phosphatase - genetics; Alkaline Phosphatase - metabolism; Biobanks; Biology and Life Sciences; Body Composition; Body fat; Body mass; Body Mass Index; Body size; Cohort analysis; Cohort Studies; Confidence intervals; Diabetes; Diabetes mellitus; Enzymes; Fat-free body mass; Female; gamma-Glutamyltransferase - genetics; gamma-Glutamyltransferase - metabolism; Genetic diversity; Genetic variance; Genetics; Genomes; Hand Strength; Humans; Linear Models; Liver; Liver - enzymology; Liver diseases; Male; Maternal & child health; Medicine; Medicine and Health Sciences; Mendelian Randomization Analysis; Muscles; People and Places; Phosphatases; Physiological aspects; Plasma; Polymorphism, Single Nucleotide; Public health; Randomization; Regression analysis; Research and Analysis Methods; Socioeconomic factors; Statistical analysis; Studies; Transaminase; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0228737

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. 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. 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. ALT reducing fat-free mass provides a possible pathway for the positive association of ALT with diabetes and suggests a potential target of intervention.