Prevalence of UGT1A6 polymorphisms in children with epilepsy on valproate monotherapy.
BACKGROUND
Valproate is a commonly used anticonvulsant drug. Uridine 5΄-diphospho (UDP)-glucuronosyltransferase (UGT) contributes to around 50% of valproate metabolism and its polymorphisms may be important for explaining the considerable variation in valproate levels in patients with epilepsy.


OBJECTIVE
This study was aimed to analyze the genetic polymorphisms of UGT1A6 in Indian children with epilepsy and their potential influence on the pharmacokinetics of valproate.


METHODS
This cross-sectional study was carried out in the Department of Pediatrics, All India Institutes of Medical Sciences (AIIMS), New Delhi, between March 2011 and July 2012.


METHODS
Children aged 3-12 years diagnosed with epilepsy on valproate monotherapy for at least 1 month were enrolled. They underwent a detailed clinical examination. The UGT1A6 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Random samples were checked by genetic sequencing. The steady-state plasma concentrations of valproate were measured by High Performance Liquid Chromatography (HPLC) and associated with UGT1A6 polymorphisms.


RESULTS
A total of 80 children were studied. The prevalence of UGT1A6 T19G was as follows: TT (45%), TG (38.8%), and GG (16.3%); that of UGT1A6 A541G was: AA (48.8%), AG (38.8%), and GG (12.5%); and that of UGT1A6 A552C was: AA (43.8%), AC (40%), and CC (16.3%). The association between valproate doses or standardized serum valproate concentration and the various UGT1A6 genotypes could not be studied reliably in this small study population.


CONCLUSIONS
The frequencies of UGT1A6 geneotypes and alleles were reported in the study population.
Puneet
P
Jain
Shivaram
S
Shastri
Department of Pediatrics, Division of Pediatric Neurology, All India Institute of Medical Sciences, New Delhi, India.
Sheffali
S
Gulati
Thomas
T
Kaleekal
Madhulika
M
Kabra
Neerja
N
Gupta
Y K
YK
Gupta
Ravindra Mohan
RM
Pandey
D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014635:Valproic Acid / Q000097:blood / Q000627:therapeutic use*
D000927:Anticonvulsants; D014635:Valproic Acid; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase