title: Effect of the PPARG2 Pro12Ala polymorphism and clinical risk factors for diabetes mellitus on HbA1c in the Japanese general population.
abstract: BACKGROUND
  Although the peroxisome proliferator-activated receptor-γ2 (PPARG2) Pro12Ala gene variant is associated with diabetes mellitus, the associations and interactions of this polymorphism and known clinical risk factors with glycated hemoglobin (HbA1c) remain poorly understood. We investigated if carrying the Ala allele was inversely associated with HbA1c level and examined possible interactions.
  
  
  METHODS
  This cross-sectional analysis used data collected from 1281 men and 1356 women aged 40 to 69 years who completed the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. PPARG2 polymorphism was determined by multiplex polymerase chain reaction (PCR)-based Invader assay. Multiple linear regression and ANCOVA were used to control for confounding variables (age, body mass index [BMI], energy intake, alcohol, smoking, physical activity, and family history of diabetes) and examine possible interactions.
  
  
  RESULTS
  After adjustment, the Ala allele was significantly inversely associated with HbA1c in women but not in men. Older age, BMI, and family history of diabetes were associated with higher HbA1c in both sexes. When stratified by PPARG2 genotype, these associations were observed in subjects with the Pro12Pro genotype but not in Ala allele carriers. A significant interaction of genotype and BMI on HbA1c was observed in women. Older age, BMI, and family history of diabetes were significantly associated with high-normal HbA1c (≥5.7% NGSP), whereas PPARG2 polymorphism was not.
  
  
  CONCLUSIONS
  Although PPARG2 Pro12Ala polymorphism might attenuate associations between known risk factors and HbA1c level, it had a small effect on high-normal HbA1c, as compared with clinical risk factors, in the general population.
authors.affiliation: Department of Preventive Medicine, Saga University, Saga, Japan. harameg@cc.saga-u.ac.jp
authors.forename: Megumi
authors.initials: M
authors.lastname: Hara
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Higaki
authors.forename: Naoto
authors.initials: N
authors.lastname: Taguchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Shinchi
authors.forename: Emi
authors.initials: E
authors.lastname: Morita
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takashima
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nakamura
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Uemura
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishida
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.forename: Haruo
authors.initials: H
authors.lastname: Mikami
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D006442:Glycated Hemoglobin; D047495:PPAR gamma; C517652:hemoglobin A1c protein, human