Diabetic nephropathy is associated with the 5'-end dinucleotide repeat polymorphism of the aldose reductase gene in Chinese subjects with Type 2 diabetes.
OBJECTIVE
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.
Liu
Y F
YF
Department of Medicine, University of Hong Kong, Hong Kong.
Wat
N M S
NM
Chung
S S M
SS
Ko
B C B
BC
Lam
K S L
KS
D020121:5' Untranslated Regions / Q000235:genetics; D000419:Albuminuria / Q000235:genetics; D000449:Aldehyde Reductase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D018900:Dinucleotide Repeats; D005260:Female; D006723:Hong Kong / Q000208:ethnology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors
D020121:5' Untranslated Regions; D000449:Aldehyde Reductase