title: Aldose reductase gene is associated with diabetic macroangiopathy in Japanese Type 2 diabetic patients.
abstract: OBJECTIVE
  The aldose reductase (AR) gene, a rate-limiting enzyme of the polyol pathway, has been investigated as a candidate gene in determining susceptibility to diabetic microangiopathy. However, the association of the AR gene with diabetic macroangiopathy has not been investigated. Therefore, the present study was conducted to determine whether genetic variations of AR may determine susceptibility to diabetic macroangiopathy.
  
  
  METHODS
  There were 378 Type 2 diabetic patients enrolled in this study. A single nucleotide polymorphism in the promoter region (C-106T) was genotyped and the AR protein content of erythrocytes measured by ELISA.
  
  
  RESULTS
  There were no significant differences in genotypic or allelic distribution in patients with or without ischaemic heart diseases, but there was a significant increase in the frequency of the CT + TT genotype and T allele in patients with stroke (P = 0.019 and P = 0.012). The erythrocyte AR protein content was increased in patients with the CT and TT genotype compared with those with the CC genotype. After adjustment for age, duration of diabetes, body mass index, systolic blood pressure, HbA1c, and serum creatinine, triglycerides, and total cholesterol in multivariate logistic-regression models, the association between this AR genotype and stroke remained significant.
  
  
  CONCLUSIONS
  Our results suggest that the CT or TT genotype of the AR gene might be a genetic marker of susceptibility to stroke in Type 2 diabetic patients. This observation might contribute to the development of strategies for the prevention of stroke in Type 2 diabetic patients.
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Watarai
authors.forename: E
authors.initials: E
authors.lastname: Nakashima
authors.forename: Y
authors.initials: Y
authors.lastname: Hamada
authors.forename: G
authors.initials: G
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Naruse
authors.forename: K
authors.initials: K
authors.lastname: Miwa
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Kamiya
authors.forename: M
authors.initials: M
authors.lastname: Nakae
authors.forename: N
authors.initials: N
authors.lastname: Hamajima
authors.forename: Y
authors.initials: Y
authors.lastname: Sekido
authors.forename: T
authors.initials: T
authors.lastname: Niwa
authors.forename: Y
authors.initials: Y
authors.lastname: Oiso
authors.forename: J
authors.initials: J
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000449:Aldehyde Reductase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D000449:Aldehyde Reductase