Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: A large meta-analysed population-based study

Karani S. Vimaleswaran, Alana Cavadino, Niek Verweij, Ilja M. Nolte, Irene Mateo Leach, Juha Auvinen, Juha Veijola, Paul Elliott, Brenda W. Penninx, Harold Snieder, Marjo Riitta Järvelin, Pim Van Der Harst, Robert D. Cohen, Barbara J. Boucher, Elina Hyppönen, Behrooz Z. Alizadeh, Paul I.W. De Bakker, H. Marike Boezen, P. V.D. Harst, Gerjan NavisMarianne Rots, H. Snieder, Ronald P. Stolk, Morris Swertz, Bruce H.R. Wolffenbuttel, Cisca Wijmenga

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7 Citations (Scopus)


Background and objective: Given the role of uncoupling protein 2 (UCP2) in the accumulation offat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (n=20 242). Design and methods: The study populations included the Northern Finland Birth Cohort 1966 (n=4996), Netherlands Study of Depression and Anxiety (n=1883) and LifeLines Cohort Study (n=13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test. Results: In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype (Pinteraction=0.03 and 0.007, respectively; adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations). Conclusion: In conclusion, our findings in 20 242 individuals suggest that UCP2 gene polymorphisms may cause liver dysfunction through the interaction with body fat rather than alcohol intake.

Original languageEnglish
Pages (from-to)863-872
Number of pages10
JournalEuropean journal of endocrinology
Issue number6
Publication statusPublished or Issued - Dec 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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