Sulfonylurea receptor gene 16-3 polymorphism - association with sulfonylurea or insulin treatment in type 2 diabetic subjects.
BACKGROUND
The presence of a complex phenotype of type 2 diabetes results from impaired insulin secretion and action, whereas the mechanism of action of sulfonylurea derivatives, most commonly used in the treatment of type 2 diabetes, is based on their ability to directly inhibit the ATP-sensitive potassium channel (KATP), which leads to b-cell depolarization, subsequent influx of calcium and then insulin exocytosis. It has recently been demonstrated in healthy subjects that molecular variants of the gene encoding for the KATP subunit - sulfonylurea receptor gene (SUR1) are associated with a decreased response of insulin secretion to intravenous injection of tolbutamide, a sulfonylurea derivative. In this study we tested whether a molecular variant of the SUR1 gene, 16-3t, has a different distribution in type 2 diabetic patients with early failure of sulfonylurea therapy, compared to patients treatable with sulfonylurea despite long diabetes duration.


METHODS
The SUR1 polymorphism was genotyped in 68 type 2 diabetic patients who required insulin treatment and had known diabetes duration L 5 years, compared to 99 patients receiving oral agents (sulfonylurea alone or in combination with metformin or acarbose) with known diabetes duration of at least 15 years.


RESULTS
We observed no significant differences in SUR1 16-3t genotype distributions or allele frequencies between the two examined groups.


CONCLUSIONS
Our study provides evidence against a major impact of the SUR1 c16-3t polymorphism on the long-term effectiveness of therapy with sulfonylurea derivatives in type 2 diabetic patients.
Department and Clinic of Internal Medicine and Diabetology, Silesian Medical University, Zabrze, Poland.
Marcin J
MJ
Zychma
Janusz
J
Gumprecht
Krzysztof
K
Strojek
Władysław
W
Grzeszczak
Dariusz
D
Moczulski
Wanda
W
Trautsolt
Dariusz
D
Karasek
D018528:ATP-Binding Cassette Transporters; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D011044:Poland; D011110:Polymorphism, Genetic; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000235:genetics* / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D064233:Sulfonylurea Receptors; D016896:Treatment Outcome
C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors