title: Improvements in glucose homeostasis in response to regular exercise are influenced by the PPARG Pro12Ala variant: results from the HERITAGE Family Study.
abstract: OBJECTIVE
  Exercise training improves glucose homeostasis, but large inter-individual differences are reported, suggesting a role of genetic factors. We investigated whether variants either confirmed or newly identified as diabetes susceptibility variants through genome-wide association studies (GWAS) modulate changes in phenotypes derived from an IVGTT in response to an endurance training programme.
  
  
  METHODS
  We analysed eight polymorphisms in seven type 2 diabetes genes (CDKAL1 rs7756992; CDKN2A and CDKN2B rs10811661 and rs564398; HHEX rs7923837; IGF2BP2 rs4402960; KCNJ11 rs5215; PPARG rs1801282; and TCF7L2 rs7903146) in a maximum of 481 sedentary, non-diabetic white individuals, who participated in a 20-week endurance training programme. Associations were tested between the variants and changes in IVGTT-derived phenotypes.
  
  
  RESULTS
  The only evidence of association with training response was found with PPARG rs1801282 (Pro12Ala). We observed that Ala carriers experienced greater increase in overall glucose tolerance (Deltaglucose disappearance index Ala/Ala 0.22 +/- 0.22, Pro/Ala 0.14 +/- 0.06, Pro/Pro 0.004 +/- 0.03; p = 0.0008), glucose effectiveness (Ala/Ala 0.28 +/- 0.41, Pro/Ala 0.44 +/- 0.14, Pro/Pro 0.09 +/- 0.06; p = 0.004), acute insulin response to glucose (Ala/Ala 64.21 +/- 37.73, Pro/Ala -11.92 +/- 40.30, Pro/Pro -46.30 +/- 14.70; p = 0.03) and disposition index (Ala/Ala 551.8 +/- 448.5, Pro/Ala 534.6 +/- 218.3, Pro/Pro -7.44 +/- 88.18; p = 0.003).
  
  
  CONCLUSIONS
  Compared with Pro/Pro individuals, PPARG Ala carriers experienced greater improvements in glucose and insulin metabolism in response to regular endurance training. However, we did not find evidence of association between type 2 diabetes susceptibility variants recently identified through GWAS and glucose homeostasis response to exercise. Our results extend those of previous studies showing that Ala carriers appear to be more responsive to beneficial health effects of lifestyle interventions.
authors.affiliation: Department of Social and Preventive Medicine, PEPS-Laval University, 2300 rue de Terrasse, Quebec, QC, Canada G1V 0A6.
authors.forename: S-M
authors.initials: SM
authors.lastname: Ruchat
authors.forename: T
authors.initials: T
authors.lastname: Rankinen
authors.forename: S J
authors.initials: SJ
authors.lastname: Weisnagel
authors.forename: T
authors.initials: T
authors.lastname: Rice
authors.forename: D C
authors.initials: DC
authors.lastname: Rao
authors.forename: R N
authors.initials: RN
authors.lastname: Bergman
authors.forename: C
authors.initials: C
authors.lastname: Bouchard
authors.forename: L
authors.initials: L
authors.lastname: Pérusse
mesh_terms: D019943:Amino Acid Substitution; D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics / Q000523:psychology; D015444:Exercise / Q000502:physiology*; D005190:Family; D005787:Gene Frequency; D019942:Genes, p16; D014644:Genetic Variation; D005838:Genotype; D018149:Glucose Intolerance / Q000097:blood / Q000235:genetics; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D008019:Life Style; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D018971:Insulin-Like Growth Factor Binding Protein 2; D047495:PPAR gamma