title: PPAR-gamma2 pro12Ala polymorphism is associated with post-challenge abnormalities of glucose homeostasis in children and adolescents with obesity.
abstract: OBJECTIVE
  The aim of the study was to investigate the association between PPAR-gamma2 Pro12Ala polymorphism and laboratory characteristics of carbohydrate metabolism in children and adolescents with obesity. In addition, serum levels of tumor necrosis factor (TNF)-alpha, and soluble form of its receptors (sTNFR1 and sTNFR2) were assessed.
  
  
  METHODS
  In a cross-sectional study, 79 obese children and adolescents of Caucasian origin were investigated. PPAR-gamma2 Pro12Ala polymorphism was determined using polymerase chain reaction--restriction fragment length polymorphism technique. Serum levels of TNF-alpha, sTNFR1 and sTNFR2 were measured by enzyme amplified sensitivity immunoassay.
  
  
  RESULTS
  The minor Ala allele frequency was found to be 14.56% in our cohort. No significant differences in age, BMI, waist circumference, blood pressure, serum lipid, uric acid, TNF-alpha, sTNFR1 and sTNFR2 values were found between carriers of the Ala allele (Pro/Ala and Ala/Ala; n=21) vs. homozygous carriers of the Pro allele (Pro/Pro; n=58). However, post-challenge (120 min) plasma glucose and insulin values were significantly lower in Ala allele carriers vs. homozygous Pro allele carriers (6.56 +/- 0.26 vs. 7.36 +/- 0.25 mmol/L and 65.9 +/- 13.8 vs. 111.8 +/- 20.7 microU/mL, respectively; p < 0.05); while no significant differences were found at fasting state.
  
  
  CONCLUSIONS
  The association between PPAR-gamma2 Prol2Ala polymorphism and glucose metabolism is already present in children and adolescents with obesity who might be at the very beginning of the natural course of type 2 diabetes. At this stage, higher insulin sensitivity can be detected in Ala allele carriers compared to homozygous Pro subjects at post-challenge but not in fasting state; however, the TNF-system seems not to be involved in the alteration of glucose homeostasis due to PPAR-gamma2 Pro12Ala polymorphism.
authors.affiliation: 1st Department of Paediatrics, Semmelweis University, Budapest, Hungary. jermendy@gmail.com
authors.forename: Agnes
authors.initials: A
authors.lastname: Jermendy
authors.forename: Anna
authors.initials: A
authors.lastname: Körner
authors.forename: Margit
authors.initials: M
authors.lastname: Kovács
authors.forename: László
authors.initials: L
authors.lastname: Madácsy
authors.forename: Károly
authors.initials: K
authors.lastname: Cseh
mesh_terms: D000293:Adolescent; D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D002648:Child; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000378:metabolism* / Q000502:physiology; D044882:Glucose Metabolism Disorders / Q000150:complications / Q000235:genetics*; D005951:Glucose Tolerance Test / Q000009:adverse effects; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011392:Proline / Q000235:genetics
chemical_list: D047495:PPAR gamma; D011392:Proline; D005947:Glucose; D000409:Alanine