TO EXPLORE THE ASSOCIATION OF CYP2C9 ALLELES IN TYPE 2 DIABETIC PATIENTS EXPERIENCING ADVERSE DRUG REACTION DUE TO SULFONYL UREA TREATMENT

Aim: To explore the association of CYP2C9 genetic polymorphism in Type2 diabetic patient under the treatment of sulfonylurea (glimepiride) and undergoing adverse drug reactions (ADRs) Glimepiride, a sulfonylurea hypoglycemic agent, is metabolized by cytochrome P450 2C9 (CYP2C9) which is known to have genetic polymorphisms. The most frequent polymorphism is the single nucleotide polymorphism (SNP) which describes the occurrence of at least 2 different alleles for one gene differing only at one specific DNA position Studies shows that CYP2C91*,CYP2C9*2 and CYP2C9*3 are the most important known alleles of CYP2C9. The wild type allele CYP2C91* is with normal enzyme activity CYP2C92*allele has a nucleoside change from cytosine to thiamine at gene position 3608 and hence causes a substitution of arginine by cysteine at protein position144; it has only minor effect on substrate affinity. In CYP2C93* allele nucleoside change from adenine to cytosine at gene position 42614 , results in an amino acid substitution of isoleucine by leucine at protein position 359 this substitution results in a loss up to 70 % of the enzyme activity with CYP2C93* allele as compared with the wild type allele CYP2C91* Patient possessing a decreased enzyme activity because of its genetic disposition, will have a higher bioavailability and smaller clearance for drugs metabolized via this specific CYP. Impaired metabolism of sulfonylurea due to gene polymorphism in the metabolic enzyme CYP2C9 might lead to adverse drug reaction like hypoglycaemia, so genotyping of CYP2C9 may thus serve as a useful tool for predicting adverse effects caused by sulfonylurea and thus helps the clinicians for safer prescribing of oral hypoglycaemic agents. Material And Methods: Type2 diabetic patients of Guwahati Medical College Hospital, Assam under the treatment of sulfonylurea (glimepiride) was identified.70 patients with glimepiride treatment at a dose of 2mg once daily and undergoing therapy from day 1(one) to 2 ye