title: The association of aldose reductase gene (AKR1B1) polymorphisms with diabetic neuropathy in adolescents.
abstract: OBJECTIVE
  Variants in the aldose reductase gene (AKR1B1) have been implicated in the development of diabetic retinopathy and nephropathy, with the most convincing data identifying a (CA)(n) repeat microsatellite allele (Z-2), which has a functional role in gene expression. In this study the association between polymorphisms in the AKR1B1 gene and diabetic neuropathy was investigated.
  
  
  METHODS
  The pupillary response to light was used as the major outcome in this study along with abnormal hot thermal threshold. Three hundred and sixty-three adolescents underwent genotyping of the AKR1B1 gene. The microsatellite (CA)(n) repeat was sequenced and two single nucleotide polymorphisms, -106C-->T and -12C-->G, were investigated by restriction fragment length polymorphism.
  
  
  RESULTS
  Seventy-six percent of participants had pupillary abnormalities (45% with two, 15% with three abnormalities). Presence of the Z-2/Z-2 genotype increased the risk nearly three-fold for pupillary abnormalities [odds ratio (OR) 3.02, 95% confidence interval (CI) 1.14, 7.98). The susceptibility genotypes (Z-2/Z-2 with -106C/-106C, Z-2/Z with -106C/-106C or Z/Z with -106C/-106C) were associated with resting pupil diameter abnormalities when compared with the protective genotypes (Z+2/Z+2 or -106T/-106T) (OR 2.83, 95% CI 1.25, 6.41). The combination of Z+2/-106T reduced the risk of abnormal heat discrimination (OR 0.48, 95% CI 0.23, 0.99).
  
  
  CONCLUSIONS
  In this study we have shown that Z-2/Z-2 genotype is significantly associated with the development of pupillary abnormality, an early indicator of diabetic autonomic neuropathy, in adolescent Australian patients with Type 1 diabetes.
authors.affiliation: Institute of Endocrinology and Diabetes, Children's Hospital at Westmead, New South Wales, Australia. kimd@chw.edu.au
authors.forename: K C
authors.initials: KC
authors.lastname: Donaghue
authors.forename: S H
authors.initials: SH
authors.lastname: Margan
authors.forename: A K F
authors.initials: AK
authors.lastname: Chan
authors.forename: B
authors.initials: B
authors.lastname: Holloway
authors.forename: M
authors.initials: M
authors.lastname: Silink
authors.forename: T
authors.initials: T
authors.lastname: Rangel
authors.forename: B
authors.initials: B
authors.lastname: Bennetts
mesh_terms: D000293:Adolescent; D000449:Aldehyde Reductase / Q000235:genetics*; D000074408:Aldo-Keto Reductases; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003929:Diabetic Neuropathies / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011680:Pupil; D012025:Reflex, Pupillary / Q000235:genetics
chemical_list: C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase