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Aldose reductase gene polymorphism is associated with progression of diabetic nephropathy in Japanese patients with type 1 diabetes mellitus
Author(s) -
Yamamoto T.,
Sato T.,
Hosoi M.,
Yoshioka K.,
Tanaka S.,
Tahara H.,
Nishizawa Y.,
Fujii S.
Publication year - 2003
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1046/j.1463-1326.2003.00243.x
Subject(s) - medicine , allele , nephropathy , retinopathy , microalbuminuria , diabetic nephropathy , diabetes mellitus , gastroenterology , endocrinology , type 2 diabetes , diabetic retinopathy , biology , genetics , gene
Aim: 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.