−429T/C and −374T/A Polymorphisms of RAGE Gene Promoter Are Not Associated With Diabetic Retinopathy in Chinese Patients With Type 2 Diabetes

The interaction between advanced glycation end products (AGEs) and the cellular receptor of AGE (RAGE) could result in cellular activation and imflammation (1). In vitro and in vivo studies indicate that RAGE plays a important role in the pathogenesis of diabetic vascular complications (2). It is plausible that genetic differences in the RAGE gene could alter expression and function to affect disease development. Many polymorphisms in the RAGE gene have already been identified (3) and show no association with macro- or microvasculopathy of diabetes (4,5). However, Hudson et al. (6) have detected two polymorphisms, −429T/C and −374T/A, in RAGE gene promoters. They reported that the −429T/C polymorphism is associated with diabetic retinopathy in type 2 diabetic patients, but found no association between the two polymorphisms and macrovascular diseases (7).

We screened the −429T/C and −374T/A polymorphisms among 212 unrelated Chinese nondiabetic subjects and 357 type 2 diabetic subjects (205 with and 152 without diabetic retinopathy). Type 2 diabetes was diagnosed according to 1999 World Health Organization criteria. Retinopathy was defined by an opthamologist. Genotyping was performed by PCR fragment-length polymorphism assay. Primers were designed according to the method of Hudson et al. (6).

There were no differences in allele frequencies between diabetic subjects with (−429T 90.1%, C 9.9%; −374T 86.4%, A 13.6%) or without (−429T 87.8%, 12.2%; −374T 87.3%, 12.7) diabetic retinopathy. No differences were found between the diabetic and nondiabetic subjects (−429T 87.3%, 12.7%; −374T 86.1%, 13.9%). The −429C and −374A allele frequencies (12.7 and 13.9%, respectively) are lower than those in Caucasians (18 and 20%) (7).

Our study indicates that the −429T/C and −374T/A polymorphisms in RAGE gene promoters are not associated with diabetic retinopathy in Chinese patients with type 2 diabetes. However, further studies on large populations are still required to evaluate whether these polymorphisms and other polymorphisms in RAGE genes are related to diabetic vascular complications.