Additive effect of aldose reductase Z-4 microsatellite polymorphism and glycaemic control on cataract development in type 2 diabetes

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.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.Of the 5823 patients analyzed, 28.1% had cataracts. After adjusting for conventional risk factors and using non-z-4 carriers with HbA1c8.0% 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 HbA1c8.0%[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).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.