C-106T polymorphism in promoter of aldose reductase gene is a risk factor for diabetic nephropathy in type 2 diabetes patients with poor glycaemic control.
BACKGROUND
Excessive flux through the polyol pathway has long been thought to be involved in the pathogenesis of diabetic microvascular complications. Aldose reductase (AR) is the first and rate-limiting enzyme in the pathway that catalyses the reduction of glucose to sorbitol. A frequent C-106T polymorphism in the promoter of the AR gene has been described, which may change the expression of the gene. The aim of the study was to examine if the C-106T polymorphism was associated with diabetic nephropathy.


METHODS
We collected 444 patients with type 2 diabetes and divided them into three groups according to the renal status: 162 patients with normoalbuminuria, 153 with microalbuminuria and 129 with persistent proteinuria. Each subject was genotyped for the C-106 polymorphism using the PCR-based RFLP protocol.


RESULTS
When the whole study population was analysed, no distortion in the genotype frequency among the study groups was observed. When we stratified the study population by HbA1c we found that in patients with HbA1c > or =9% (median) the CT and TT genotypes were more frequent in patients with diabetic nephropathy (proteinuria and microalbuminuria) than those with normoalbuminuria (OR 2.04, 95% CI 1.12-3.74).


CONCLUSIONS
The C-106T polymorphism in the AR gene is a risk factor for development of diabetic nephropathy in type 2 diabetes in patients with poor glycaemic control.
Gosek
Katarzyna
K
Department and Clinic of Internal Medicine, Diabetology and Nephrology, Silesian School of Medicine, Zabrze, Poland. kasiagos@poczta.onet.pl
Moczulski
Dariusz
D
Zukowska-Szczechowska
Ewa
E
Grzeszczak
Wladyslaw
W
D000368:Aged; D000419:Albuminuria / Q000235:genetics; D000449:Aldehyde Reductase / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D000449:Aldehyde Reductase; D001786:Blood Glucose; D006442:Glycated Hemoglobin