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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
Tetsuya
T
Makiishi
Shin-ichi
S
Araki
Daisuke
D
Koya
Shiro
S
Maeda
Atsunori
A
Kashiwagi
Masakazu
M
Haneda
D000368:Aged; D000449:Aldehyde Reductase / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000235:genetics*; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D013223:Statistics as Topic
D000449:Aldehyde Reductase