TY  - JOUR
AU  - Kvaloy, K.
AU  - Holmen, J.
AU  - Hveem, K.
AU  - Holmen, T. L.
PY  - 2015
DA  - 2015//
TI  - Genetic Effects on Longitudinal Changes from Healthy to Adverse Weight and Metabolic Status – The HUNT Study
T2  - PloS one
JO  - PLoS One
SP  - e0139632
VL  - 10
IS  - 10
CY  - HUNT Research Center, Department of Public Health and General Practice, Faculty of Medicine, Norwegi
KW  - HUNT2
KW  - HUNT3
KW  - Adolescent
KW  - Adult
KW  - Apolipoproteins A/genetics
KW  - Blood Glucose/analysis
KW  - Blood Pressure
KW  - Body Mass Index
KW  - Cholesterol
KW  - HDL/blood
KW  - Cross-Sectional Studies
KW  - Female
KW  - Humans
KW  - Longitudinal Studies
KW  - Male
KW  - Metabolic Syndrome X/blood/*etiology/genetics
KW  - Middle Aged
KW  - Overweight/blood/*complications/*genetics
KW  - *Polymorphism
KW  - Single Nucleotide
KW  - Proteins/genetics
KW  - Receptors
KW  - Dopamine D2/genetics
KW  - Triglycerides/blood
KW  - Weight Gain
KW  - Young Adult
AB  - INTRODUCTION: The complexity of obesity and onset and susceptibility of cardio-metabolic disorders are still poorly understood and is addressed here through studies of genetic influence on weight gain and increased metabolic risk longitudinally. SUBJECTS/METHODS: Twenty seven previously identified obesity, eating disorder or metabolic risk susceptibility SNPs were tested for association with weight or metabolically related traits longitudinally in 3999 adults participating both in the HUNT2 (1995-97) and HUNT3 (2006-08) surveys. Regression analyses were performed with changes from normal weight to overweight/obesity or from metabolically healthy to adverse developments with regards to blood pressure, glucose, HDL cholesterol, triglycerides or metabolic syndrome as outcomes. Additionally, a sub-sample of 1380 adolescents was included for testing association of nine SNPs with longitudinal weight gain into young adulthood. RESULTS: The most substantial effect on BMI-based weight gain from normal to overweight/obesity in adults was observed for the DRD2 variant (rs6277)(OR: 0.79, 95% CI: 0.69-0.90, P = 3.9x10-4, adj. P = 0.015). DRD2 was not associated with BMI on a cross-sectional level. In the adolescent sample, FTO (rs1121980) was associated with change to overweight at adulthood in the combined male-female sample (OR: 1.27, 95% CI: 1.09-1.49, P = 3.0x10-3, adj. P = 0.019) and in females (OR: 1.53, 95% CI: 1.23-1.91, P = 1.8x10-4, adj. P = 0.003). When testing for association to longitudinal adverse developments with regard to blood pressure, blood lipids and glucose, only rs964184 (ZNF259/APOA5) was significantly associated to unfavourable triglyceride changes (OR: 1.66, 95% CI: 1.36-2.03, P = 5.7x10-7, adj. P = 0.001). Pleiotropic effects on metabolic traits, however, were observed for several genetic loci cross-sectionally, ZNF259/APOA5, LPL and GRB14 being the most important. CONCLUSIONS: DRD2 exhibits effects on weight gain from normal weight to overweight/obesity in adults, while, FTO is associated to weight gain from adolescence to young adulthood. Unhealthy longitudinal triglyceride development is strongly affected by ZNF259/APOA. Our main finding, linking the DRD2 variant directly to the longitudinal weight gain observed, has not previously been identified. It suggests a genetic pre-disposition involving the dopaminergic signalling pathways known to play a role in food reward and satiety linked mechanisms.
UR  - http://www.ncbi.nlm.nih.gov/pubmed/26445370
UR  - https://doi.org/10.1371/journal.pone.0139632
DO  - 10.1371/journal.pone.0139632
N1  - Kvaloy, KirstiHolmen, JosteinHveem, KristianHolmen, Turid Lingaaseng2015/10/09 06:00PLoS One. 2015 Oct 7;10(10):e0139632. doi: 10.1371/journal.pone.0139632. eCollection 2015.
ID  - Kvaloy_etal2015
ER  -