Abstract
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.
| Language | English |
|---|---|
| Pages | 863-872 |
| Number of pages | 10 |
| Journal | European Journal of Endocrinology |
| Volume | 173 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 1 Jan 2015 |
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrinology
Cite this
}
Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function : A large meta-analysed population-based study. / Vimaleswaran, Karani S.; Cavadino, Alana; Verweij, Niek; Nolte, Ilja M.; Leach, Irene Mateo; Auvinen, Juha; Veijola, Juha; Elliott, Paul; Penninx, Brenda W.; Snieder, Harold; Järvelin, Marjo Riitta; Van Der Harst, Pim; Cohen, Robert D.; Boucher, Barbara J.; Hyppönen, Elina; Alizadeh, Behrooz Z.; De Bakker, Paul I.W.; Boezen, H. Marike; Harst, P. V.D.; Navis, Gerjan; Rots, Marianne; Snieder, H.; Stolk, Ronald P.; Swertz, Morris; Wolffenbuttel, Bruce H.R.; Wijmenga, Cisca.
In: European Journal of Endocrinology, Vol. 173, No. 6, 01.01.2015, p. 863-872.Research output: Contribution to journal › Article
TY - JOUR
T1 - Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function
T2 - European Journal of Endocrinology
AU - Vimaleswaran, Karani S.
AU - Cavadino, Alana
AU - Verweij, Niek
AU - Nolte, Ilja M.
AU - Leach, Irene Mateo
AU - Auvinen, Juha
AU - Veijola, Juha
AU - Elliott, Paul
AU - Penninx, Brenda W.
AU - Snieder, Harold
AU - Järvelin, Marjo Riitta
AU - Van Der Harst, Pim
AU - Cohen, Robert D.
AU - Boucher, Barbara J.
AU - Hyppönen, Elina
AU - Alizadeh, Behrooz Z.
AU - De Bakker, Paul I.W.
AU - Boezen, H. Marike
AU - Harst, P. V.D.
AU - Navis, Gerjan
AU - Rots, Marianne
AU - Snieder, H.
AU - Stolk, Ronald P.
AU - Swertz, Morris
AU - Wolffenbuttel, Bruce H.R.
AU - Wijmenga, Cisca
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84947914548&partnerID=8YFLogxK
U2 - 10.1530/EJE-15-0839
DO - 10.1530/EJE-15-0839
M3 - Article
VL - 173
SP - 863
EP - 872
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 6
ER -