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01.12.2016 | Research article | Ausgabe 1/2016 Open Access

BMC Pediatrics 1/2016

Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy

Zeitschrift:
BMC Pediatrics > Ausgabe 1/2016
Autoren:
Nagendra Chaudhary, Madhulika Kabra, Sheffali Gulati, Yogendra Kumar Gupta, Ravindra Mohan Pandey, Bal Dev Bhatia
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12887-016-0603-0) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

NC designed the study, carried out the molecular genetic studies, and drafted the manuscript. MK and SG participated in designing the study, coordination and drafting the manuscript. YKG participated in laboratory analysis and manuscript drafting. RMP performed the statistical analysis. BDB was involved in supervision and drafting the manuscript. All the authors read and approved the final manuscript

Abstract

Background

Phenytoin, mainly metabolized by cytochrome P450 enzyme system, has a narrow therapeutic index and may have adverse effects due to inter-individual variation in the dose requirement and genetic polymorphisms. This cross-sectional study was done to study the prevalence of cytochrome P450 CYP2C9 polymorphisms in Indian epileptic children and to see the effect of polymorphisms on serum levels in epileptic children on phenytoin monotherapy.

Methods

We studied 89 epileptic children of North Indian population, randomly selected, to see the genotypic and allelic frequency of CYP2C9 and its association with drug levels on phenytoin monotherapy. Analysis was done using STATA 9 Software. The results were analyzed as prevalence at 95 % C.I. (Confidence Interval). The difference in mean phenytoin serum levels between wild and mutant alleles was tested using Student`s T test for independent samples. P value less than 0.05 was considered statistically significant.

Results

CYP2C9*1, *2 & *3 allelic frequencies were 85.4, 4.5 and 10.1 % respectively. CYP2C9*3 allelic group showed significantly higher serum phenytoin levels compared to the wild variants (P = 0.009). There was no statistically significant difference in the dose received (P = 0.12) and side effects of CYP2C9*2 and CYP2C9*3 genotypes (P = 0.442 and 0.597 respectively) when compared with wild variant.

Conclusion

CYP2C9*3 is more common than *2 in the present study. All the polymorphisms demonstrated in our study were heterozygous with no homozygosity. Serum phenytoin levels are higher in polymorphic groups (*3) which suggest their poor metabolizing nature. Genotyping may help to avoid toxicity and concentration-dependent adverse effects.
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