We thank Ng et al. (1) for their response to our recent article on the associations of two aldose reductase gene polymorphisms, a (CA)n microsatellite at the 5′ region and a promoter C/T polymorphism with nephropathy and retinopathy in type 2 diabetes (2).

However, we hold the view that Ng et al. have misinterpreted our data and inadvertenly commented that our “negative” results were related to our less stringent definitions of nephropathy, when in fact, we have provided clear evidence to show that both the z-2 and T allele of the aldose reductase gene polymorphisms were risk factors for diabetic nephropathy in Chinese type 2 diabetic patients.

In the consecutive cohort analysis involving all 738 type 2 diabetic patients, those with the T allele had higher albuminuria than noncarriers (30.2 vs. 21.9 μg/min) (2). This difference remained significant after adjustment for age, duration of disease, blood pressure, and HbA1c.

We then excluded patients with a short duration of disease (<5 years) and used a case-control study design to further test the hypothesis. We defined case subjects as diabetic patients with both diabetic retinopathy and nephropathy, whereas patients who had no complications were selected as control subjects. Using this design, we found that both z-2 (odds ratio 2.64) and T alleles (odds ratio 2.48) were independent risk factors for the coexistence of diabetic nephropathy and retinopathy. The other predictors were age, blood pressure, HbA1c, triglyceride, and male sex (2).

Hence, contrary to the comments made by Ng et al. that we failed to confirm results from previous studies on aldose reductase as risk genotypes for diabetic nephropathy in type 1 diabetes, our study has indeed provided corroborative evidence to support these findings.

1.
Ng DPK, Chia K-S, Koh D: Phenotypic heterogeneity and associations of two aldose reductase gene polymorphisms with nephropathy and retinopathy in type 2 diabetes (Letter).
Diabetes Care
27
:
289
–290,
2004
2.
Wang Y, Ng MCY, Lee SC, So WY, Tong CY, Cockram CS, Critchley JAJH, Chan JCN: Phenotypic heterogeneity and associations of two aldose reductase gene polymorphisms with nephropathy and retinopathy in type 2 diabetes.
Diabetes Care
26
:
2410
–2415,
2003