Diabetic nephropathy is associated with the 5'-end dinucleotide repeat polymorphism of the aldose reductase gene in Chinese subjects with Type 2 diabetes

Diabet Med. 2002 Feb;19(2):113-8. doi: 10.1046/j.1464-5491.2002.00632.x.

Abstract

Aims: We investigated whether the promoter dinucleotide repeat polymorphism of the aldose reductase gene (5'-ALR2), implicated in the development of nephropathy in Type 1 diabetes, was associated with diabetic nephropathy in Type 2 diabetes.

Methods: In 265 Southern Chinese with Type 2 diabetes the 5' -ALR2 polymorphism was identified in genomic DNA using polymerase chain reaction and automated fluorescent scanning. They were classified as normoalbuminuric (n = 128), microalbuminuric (n = 85) or albuminuric (n = 52) according to the mean albumin excretion rate of two 12-h overnight collections.

Results: The 5' -ALR2 allele and genotype distributions differed significantly among the three groups of patients (P < 0.003 and P < 0.01, respectively). Normoalbuminuric patients had the lowest Z - 2 allele frequency: 17.6% vs. 28.2% and 23.1% for microalbuminuric and albuminuric patients, respectively, and the highest Z + 2 allele frequency: 36.7% vs. 21.2% and 23.1% in microalbuminuric and albuminuric patients, respectively. They also had the lowest Z - 2/X genotype frequency (X = any allele other than Z + 2): 18.8% vs. 36.5% in microalbuminuric (P < 0.01) and 38.5% in albuminuric patients (P < 0.02), respectively, but the highest Z + 2/Y genotype frequency (Y = any allele other than Z - 2): 50.7% vs. 27.0% and 34.6% in microalbuminuric (P < 0.001) and albuminuric patients, respectively. In a multiple logistic regression model, the Z - 2/X genotype (odds ratio 3.10; P < 0.025) was an independent risk factor of diabetic nephropathy, microalbuminuria or albuminuria, together with age, mean arterial pressure and body mass index.

Conclusions: The 5' -ALR2 dinucleotide repeat polymorphism is associated with the development of diabetic nephropathy in Southern Chinese with Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Albuminuria / genetics
  • Aldehyde Reductase / genetics*
  • Asian Continental Ancestry Group / genetics
  • Blood Pressure
  • China
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Nephropathies / genetics*
  • Dinucleotide Repeats*
  • Female
  • Hong Kong / ethnology
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Risk Factors

Substances

  • 5' Untranslated Regions
  • Aldehyde Reductase