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Frequency of Cyp2c93* allele in patients with type 2 diabetes mellitus on sulfonylurea therapy

Prasanta Kumar Bhattacharya, Bornali Dutta, Aakash Roy.

Abstract
Background: Sulfonylureas are mainstay of pharmacotherapy for type 2 diabetes mellitus (T2DM). Individual variability exists in pharmacokinetic and pharmacodynamic responses adverse effects to sulfonylurea.

Objective: To determine frequency of cytochrome P450 2C9 mutant allele CYP2C93*, in T2DM patients on sulfonylurea therapy, and to ascertain the frequency of adverse drug reactions (ADR) with respect to particular allelic distribution.

Materials and Methods: A hospital-based prospective observational study was carried out in a tertiary-care teaching hospital. Study included 136 T2DM patients on sulfonylurea therapy (83 with ≥1 ADR and 53 without ADR). DNA was isolated from the blood samples taken from all 136 patients by DNA isolation. PCR-RFLP (restriction fragment length polymorphism) technique was used for detection of CYP2C93* (Ile359Leu) allele and the wild type allele CYP2C91* by digestion with restriction enzyme. Data were analyzed using Statistical Package for Social Survey (SPSS) for Windows, version 16.0 and Microsoft Excel to determine descriptive statistics.

Result: Allele CYP2C93* was detected in 11 patients. All alleles negative for the nucleotide substitutions at position 42614 (*3) were presumed to be wild type CYP2C9*1. Among the patients with CYP2C93* allele 11 patients experienced hypoglycemia and one patient experienced acute visual disturbances. No CYP2C93* was detected in the subjects without ADR.

Conclusion: In our study CYP2C93* was identified in 11 patients experiencing hypoglycaemia and in one patient experiencing acute visual disturbances. In view of the existence of such polymorphisms and its effects on sulfonylurea therapy further studies are required to assess the magnitude of such problems in T2DM.

Key words: Sulfonylurea, adverse drug reaction, type 2 diabetes mellitus, frequency, C CYP2C93* allele


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