Aldose reductase gene polymorphism is associated with progression of diabetic nephropathy in Japanese patients with type 1 diabetes mellitus.
OBJECTIVE
The objective of this study was to investigate cross-sectionally and longitudinally whether polymorphism of the (A-C)n dinucleotide repeat sequence of the aldose reductase (AR) gene may modulate risk for diabetic nephropathy or retinopathy in Japanese patients with type 1 diabetes.


METHODS
We obtained DNA samples from 101 patients followed up after the onset of type 1 diabetes and analysed a (A-C)n dinucleotide repeat polymorphic marker in the AR gene by polymerase chain reaction (PCR) method.


RESULTS
Ten alleles ranging from Z-10 (128 bp) to Z+8 (146 bp) in repeat number were identified. In cross-sectional studies, the prevalence of the Z+2 allele was higher than that of any other allele in patients with diabetic nephropathy (37.5% of patients in a microalbuminuria group, and 41.7% of those in a macroalbuminuria group including patients with chronic renal failure and maintenance haemodialysis treatment). Prevalence of the Z+2 allele was not increased in patients with diabetic retinopathy. In longitudinal Kaplan-Meier plots, the cumulative incidence of nephropathy was significantly associated with homozygosity for the Z+2 allele (log rank test, p = 0.031); respective prevalence of nephropathy after diabetes durations of 10 and 15 years was 42.9% and 100% in Z+2 homozygotes (n = 8), 17.6% and 27.4% in Z+2 heterozygotes (n = 44), and 6.1% and 17.4% in patients without the Z+2 allele (n = 49). However, occurrence of retinopathy was not influenced by the Z+2 allele (log rank test, p = 0.926).


CONCLUSIONS
Homozygosity for the Z+2 allele was associated with accelerated early progression of diabetic nephropathy in Japanese type 1 diabetic patients.
Yamamoto
T
T
Department of Metabolism and Endocrinology, Osaka City General Hospital, Osaka, Japan. tsunehiko@sannet.ne.jp
Sato
T
T
Hosoi
M
M
Yoshioka
K
K
Tanaka
S
S
Tahara
H
H
Nishizawa
Y
Y
Fujii
S
S
D000328:Adult; D000449:Aldehyde Reductase / Q000235:genetics*; D000483:Alleles; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D000449:Aldehyde Reductase