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Common variation in the NOS1AP gene is associated with reduced glucose-lowering effect and with increased mortality in users of sulfonylurea.
- Source :
-
Pharmacogenetics and genomics [Pharmacogenet Genomics] 2008 Jul; Vol. 18 (7), pp. 591-7. - Publication Year :
- 2008
-
Abstract
- Objective: The single nucleotide polymorphism rs10494366 in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene is associated with QTc prolongation, through an effect on the intracellular Ca levels. As sulfonylurea stimulate insulin secretion by an increased influx of Ca, we hypothesized that this polymorphism is associated with the glucose-lowering effect and mortality risk in sulfonylurea users.<br />Methods: Associations between the NOS1AP polymorphism, prescribed doses, and mortality rates in sulfonylurea, metformin, and insulin users were assessed in the Rotterdam Study, a population-based cohort study of 7983 elderly people.<br />Results: We identified 619 participants who were prescribed oral antidiabetic drugs during follow-up. In glibenclamide users carrying the TG genotype, the prescribed doses were higher compared with the glibenclamide users carrying the TT genotype [0.38 defined daily dose units, 95% confidence interval (CI) 0.14-0.63]. Glibenclamide users with the TG or GG genotype had an increased mortality risk compared with glibenclamide users with the TT genotype [hazard ratio (HR) 2.80, 95% CI: 1.09-7.22]. Tolbutamide users with the TG or GG genotype (HR: 0.30, 95% CI: 0.14-0.63) and glimepiride users with the TG or GG genotype (HR: 0.18, 95% CI: 0.04-0.74) had a decreased mortality risk compared with tolbutamide and glimepiride users with the TT genotype.<br />Conclusion: In participants with the TG or GG genotype at rs10494366 in the NOS1AP gene, glibenclamide is less effective in reducing glucose levels and mortality rates were higher compared with glibenclamide users with the TT genotype. In tolbutamide and glimepiride users, the TG and GG genotype were associated with a reduced mortality rate.
- Subjects :
- Aged
Aged, 80 and over
Blood Glucose drug effects
Cohort Studies
Female
Follow-Up Studies
Genotype
Humans
Hypoglycemic Agents pharmacology
Hypoglycemic Agents therapeutic use
Male
Middle Aged
Sulfonylurea Compounds pharmacology
Survival Analysis
Adaptor Proteins, Signal Transducing genetics
Diabetes Mellitus, Type 2 drug therapy
Diabetes Mellitus, Type 2 mortality
Drug Resistance genetics
Polymorphism, Single Nucleotide
Sulfonylurea Compounds therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1744-6872
- Volume :
- 18
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Pharmacogenetics and genomics
- Publication Type :
- Academic Journal
- Accession number :
- 18551039
- Full Text :
- https://doi.org/10.1097/FPC.0b013e328300e8c5