title: Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. enagendra@hotmail.com.|Department of Pediatrics, Universal College of Medical Sciences, Bhairahawa, Nepal. enagendra@hotmail.com.
authors.forename: Nagendra
authors.initials: N
authors.lastname: Chaudhary
authors.affiliation: Genetic Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kabra
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Sheffali
authors.initials: S
authors.lastname: Gulati
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Yogendra Kumar
authors.initials: YK
authors.lastname: Gupta
authors.affiliation: Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ravindra Mohan
authors.initials: RM
authors.lastname: Pandey
authors.affiliation: Department of Pediatrics, Universal College of Medical Sciences, Bhairahawa, Nepal.
authors.forename: Bal Dev
authors.initials: BD
authors.lastname: Bhatia
mesh_terms: D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007194:India; D008297:Male; D010672:Phenytoin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011110:Polymorphism, Genetic
chemical_list: D000927:Anticonvulsants; D005819:Genetic Markers; D010672:Phenytoin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9
keywords: CYP2C9 polymorphism; Epilepsy; Neurocysticercosis; Phenytoin monotherapy