The combination of UCP3-55CT and PPARγ2Pro12Ala polymorphisms affects BMI and substrate oxidation in two diabetic populations

Nutr Metab Cardiovasc Dis. 2016 May;26(5):400-6. doi: 10.1016/j.numecd.2016.01.012. Epub 2016 Feb 22.

Abstract

Background and aim: To evaluate the combined contribution of UCP3-55CT and PPARγ2 Pro12Ala polymorphisms as correlates of BMI, energy expenditure (REE) and substrate oxidation in people with type 2 diabetes.

Methods and results: Two independent population with type 2 diabetes were studied: population A, n = 272; population B, n = 269. Based on both UCP3 and PPARγ2 genotypes three groups were created. Carriers of the PPARγ2 Pro12Ala in combination with the CC genotype of UCP3 (ProAla/CC, group 1); carriers of only one of these genotypes (either CC/ProPro or CT-TT/ProAla, group 2); people with neither variants (CT-TT/ProPro, group 3). In both populations BMI (kg/m(2)) was highest in group 1, intermediate in group 2 and lowest in group 3, independent of energy intake (i.e 35.3 ± 6.7 vs 33.4 ± 5.4 vs 31.8 ± 3, p < 0.02, population A; 32.4 ± 4.2 vs 31.7 ± 3.8 vs 30.1 ± 2.7; p < 0.03, population B). People with the ProAla/CC genotype (group 1) showed similar REE, but lower lipid oxidation (10.9 vs 13.9 g/kg fat free mass/day; p = 0.04) and higher carbohydrate oxidation (23.6 vs 15.6 g/kg fat free mass/day; p = 0.02) than carriers of other genotypes.

Conclusions: The combination of UCP3-55 CC and PPARγ2 Pro12Ala genotypes is associated with significantly higher BMI than other PPARγ2-UCP3 genotype combinations, partly due to a reduced ability in lipids oxidation. The relative importance of these mechanism(s) may be different in non diabetic people.

Keywords: BMI; Polymorphism; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / genetics*
  • Dietary Carbohydrates / metabolism*
  • Dietary Fats / metabolism*
  • Energy Metabolism / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / diagnosis
  • Obesity / genetics*
  • Oxidation-Reduction
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • Phenotype
  • Polymorphism, Genetic*
  • Uncoupling Protein 3 / genetics*
  • Uncoupling Protein 3 / metabolism
  • Weight Gain / genetics

Substances

  • Dietary Carbohydrates
  • Dietary Fats
  • PPAR gamma
  • UCP3 protein, human
  • Uncoupling Protein 3