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; LifeLines Cohort Study; 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

doi:10.1530/EJE-15-0839

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

Eur J Endocrinol. 2015 Dec;173(6):863-72. doi: 10.1530/EJE-15-0839.

Authors

Affiliations

¹ Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Readin
² Hugh Sinclair Unit of Human NutritionDepartment of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, PO Box 226, Reading RG6 6AP, UKPopulationPolicy and Practice, UCL Institute of Child Health, London, UKWolfson Institute of Preventive MedicineCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, UK, Departments of CardiologyEpidemiologyUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsUnit of Primary CareOulu University Hospital, Oulu, FinlandFaculty of MedicineCenter for Life Course EpidemiologyDepartment of PsychiatryCenter for Clinical Neuroscience, University of Oulu, Oulu, FinlandDepartment of PsychiatryMedical Research Center, University Hospital of Oulu, Oulu, FinlandDepartment of Epidemiology and BiostatisticsImperial College London, MRC-PHE Centre for Environment and Health, London, UKDepartment of PsychiatryLeiden University Medical Center, Leiden, The NetherlandsDepartment of PsychiatryEMGO Institute of Health and Care Research, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The NetherlandsBiocenter OuluUniversity of Oulu, Oulu, FinlandDepartment of GeneticsUniversity Medical Center Groningen, University of Groningen, Groningen, The NetherlandsICIN - Netherlands Heart InstituteDurrer Center for Cardiogenetic Research, Utrecht, The NetherlandsBarts and The London School of Medicine and DentistryQueen Mary University of London, Blizard Institute, Newark Street, London, UKCentre for Population Health ResearchSchool of Health Science and Sansom Institute of Health Research, University of South Australia, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research InstituteAdelaide, South Australia, Australia.

PMID: 26526553
DOI: 10.1530/EJE-15-0839

Abstract

Background and objective: Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat 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.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alanine Transaminase / metabolism*
Alcohol Drinking / metabolism*
Cohort Studies
Female
Finland
Gene-Environment Interaction*
Humans
Ion Channels / genetics*
Liver Diseases / genetics*
Liver Diseases / metabolism
Liver Function Tests
Logistic Models
Male
Middle Aged
Mitochondrial Proteins / genetics*
Netherlands
Obesity / metabolism*
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Risk Factors
Uncoupling Protein 2
gamma-Glutamyltransferase / metabolism*

Substances

Ion Channels
Mitochondrial Proteins
UCP2 protein, human
Uncoupling Protein 2
gamma-Glutamyltransferase
gamma-glutamyltransferase, human
Alanine Transaminase

Abstract

Publication types

MeSH terms

Substances

Grants and funding