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

Original Article

Author Details : Bornali Dutta, Prasanta Kr. Bhattacharya, Mangala Lahkar

Volume : 2, Issue : 2, Year : 2015

Article Page : 81-84

Abstract

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 years were possible to be identified in this 2 years of the study.32 patients had no complain for the drug but 38 patients suspected of having at least one adverse drug reaction(ADR) . Blood samples of patients experiencing ADRs as well as from patient without any complain for the drug were collected after written informed consent and prior ethical committee clearance ,reference no.MC/190/2007/Pt11/22 date:30/03/11.DNA was isolated , alleles CYP2C91*(wild type) and CYP2C92*, CYP2C93* variant form was detected by Polymerase chain reaction –Restriction fragment length polymorphism.

Results: Variant form CYP2C92*and CYP2C93* allele on both groups with and without ADR experienced during the course of therapy was studied along with the wild type CYP2C91* from the variant form. Allele CYP2C9 1*(wild type, having 80% enzyme activity) predominates in the group experiencing no any adverse drug reaction. No variant form CYP2C92* allele was able to be identified in any of the two groups whereas variant form CYP2C93* allele was identified in few samples of the group with ADRs. A test for significance (chi square test) for occurrence of allele in parameter like adverse drug reaction was done. The p value (<0.05) obtained was found to be statistically significant.

Key Words: Single nucleotide polymorphism, CYP2C9, Polymerase chain reaction, Adverse drug reaction.

How to cite : Dutta B, Bhattacharya P K, Lahkar M, TO EXPLORE THE ASSOCIATION OF CYP2C9 ALLELES IN TYPE 2 DIABETIC PATIENTS EXPERIENCING ADVERSE DRUG REACTION DUE TO SULFONYL UREA TREATMENT. Indian J Pharm Pharmacol 2015;2(2):81-84

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