title: Additive effect of aldose reductase Z-4 microsatellite polymorphism and glycaemic control on cataract development in type 2 diabetes.
abstract: OBJECTIVE
  To examine the additive effect of the z-4 microsatellite polymorphism of aldose reductase gene (ALR2) and glycaemic control on risk of cataract in a prospective cohort of Chinese type 2 diabetic patients.
  
  
  METHODS
  The (CA)n microsatellite polymorphism of ALR2 was determined using PCR followed by capillary gel electrophoresis. Cataract was defined by presence of lens opacity on direct ophthalmoscopy or history of cataract surgery. A non-linear curve approach was used to identify the threshold of glycated hemoglobin (HbA1c) at which the odds ratio (OR) for cataract started to increase. The association of z-4 allele with cataract, above and below this threshold, was assessed using multiple logistic regression analysis.
  
  
  RESULTS
  Of the 5823 patients analyzed, 28.1% had cataracts. After adjusting for conventional risk factors and using non-z-4 carriers with HbA1c<8.0% as referent group (n = 3173), the OR (95% confidence intervals) for cataract was highest in z-4 carriers with HbA1c ≥ 8.0% [1.43 (1.05-1.96), n = 244], compared to non-z-4 carriers with HbA1c ≥ 8.0 [1.27 (1.10-1.47), n = 1836] and z-4 carriers with HbA1c<8.0%[1.01 (0.77-1.29), n = 420, P(trend) < 0.001]. This additive association remained significant after additional adjustments for drug use (P(trend) = 0.002) and renal function (P(trend) = 0.01).
  
  
  CONCLUSIONS
  In type 2 diabetic patients with suboptimal glycaemic control, the z-4 allele of ALR2 (CA)n polymorphism was independently associated with increased susceptibility to cataracts.
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China. Electronic address: yingwang@cuhk.edu.hk.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors.forename: Andrea O Y
authors.initials: AO
authors.lastname: Luk
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Center for Diabetes Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.affiliation: Department of Ophthalmology and Visual Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors.forename: Calvin C P
authors.initials: CC
authors.lastname: Pang
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lam
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors.forename: Shao C
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology and Visual Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors.forename: Dennis S C
authors.initials: DS
authors.lastname: Lam
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors.forename: Ronald C W
authors.initials: RC
authors.lastname: Ma
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: So
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism*; D002386:Cataract / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D003930:Diabetic Retinopathy / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D001786:Blood Glucose; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase
keywords: Aldose reductase; Cataract; Genetic polymorphism; Glycaemic control; Type 2 diabetes