Impact of sulfonylurea receptor 1 genetic variability on non-insulin-dependent diabetes mellitus prevalence and treatment: a population study.
The high affinity sulfonylurea receptor 1 (SUR1) is involved in the metabolism of glucose in pancreatic beta-cells. We investigated the impact of the SUR1 intron 16-3t-->c polymorphism on non-insulin-dependent diabetes mellitus (NIDDM) prevalence in a large representative sample of French men and women, 35-64 years old, and explored potential relationships between the SUR1 intron 16 -t-->c polymorphism and sulfonylurea therapy efficiency. This study took place in Lille (northern), Strasbourg (eastern), and Toulouse (southern France). One hundred and twenty-two subjects with NIDDM were registered. We stratified NIDDM subjects according to their medical treatment: sulfonylureas (n = 70) versus other treatments (n = 50). From the three populations, a control group was selected (n = 1,250). Subjects carrying the cc intron 16 genotype had an increased risk of NIDDM [odds ratio (OR) = 1.76, 95% confidence interval (CI) 1.10-2.80; P = 0.017]. Subjects bearing at least one -3c allele and treated with sulfonylurea agents had fasting plasma triglyceride concentrations 35% lower than subjects that were tt homozygous (P = 0.026), whereas no difference could be detected between genotypes in NIDDM subjects treated with other treatments. The SUR1 intron 16 -3t-->c polymorphism was associated with an increased susceptibility to NIDDM in this population study, and seems to modulate the sulfonylurea therapy efficiency on hypertriglyceridemia reduction. This observation may help to better target the various therapies available for treatment of NIDDM.
Meirhaeghe
A
A
INSERM U508, Institut Pasteur de Lille, 1 rue Calmette, 59019 Lille Cedex, France.
Helbecque
N
N
Cottel
D
D
Arveiler
D
D
Ruidavets
J B
JB
Haas
B
B
Ferrières
J
J
Tauber
J P
JP
Bingham
A
A
Amouyel
P
P
D018528:ATP-Binding Cassette Transporters; D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000627:therapeutic use*; D007438:Introns; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D015995:Prevalence; D011955:Receptors, Drug / Q000235:genetics* / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000378:metabolism / Q000627:therapeutic use*; D064233:Sulfonylurea Receptors
C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors