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Am J Kidney Dis. 2003 Nov;42(5):943-51.

C-106T polymorphism of AKR1B1 is associated with diabetic nephropathy and erythrocyte aldose reductase content in Japanese subjects with type 2 diabetes mellitus.

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Department of Medicine, Shiga University of Medical Science, Shiga, Japan.



The C-106T polymorphism of AKR1B1, which encodes aldose reductase (AR), was reported to be associated with diabetic nephropathy (DN). However, this association in Japanese patients with type 2 diabetes mellitus and its potential role as a clinical marker remain unclear.


The C-106T polymorphism was genotyped in 228 cases (microalbuminuria or overt proteinuria) and 220 controls (normoalbuminuria with diabetes duration > or =10 years) for a case-control comparison, and the association with erythrocyte AR content was investigated. In addition, a new C-11G polymorphism in the promoter region of AKR1B1 was genotyped.


The distribution of genotypes of the C-106T polymorphism in cases was significantly different from that in controls (P = 0.031). Carriers of the TT genotype at the C-106T polymorphism were more frequent in cases than controls, with an odds ratio of 4.7 (95% confidence interval, 1.3 to 17). Erythrocyte AR content was significantly elevated in TT carriers in comparison to non-TT carriers (13.1 +/- 1.2 versus 10.2 +/- 1.2 ng/mg hemoglobin [Hb]; P < 0.001) and in cases in comparison to controls (10.6 +/- 1.3 versus 10.1 +/- 1.2 ng/mg Hb; P = 0.041). However, distribution of genotypes of the C-11G polymorphism and estimated frequencies of haplotypes defined by these 2 polymorphisms did not differ between cases and controls.


The TT genotype of the C-106T polymorphism of AKR1B1 increases the risk for DN in Japanese subjects with type 2 diabetes mellitus, which could be linked in part to greater expression of AR.

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