SCN1A IVS5N+5 polymorphism and response to sodium valproate: a multicenter study.
OBJECTIVE
Approximately 30% of epilepsy patients do not response to antiepileptic drugs (AEDs). The functional SCN1A IVS5N+5 polymorphism may play a role in response to some AEDs. The purpose of this study was to examine this hypothesis in a cohort study of Malaysian and Hong Kong Chinese epilepsy patients on sodium valproate (VPA) monotherapy and in a meta-analysis.


METHODS
The SCN1A IVS5N+5 polymorphism was genotyped in 583 Malaysian (84%) and Hong Kong Chinese (16%) epilepsy patients receiving VPA monotherapy. The related association studies, including the current study, were meta-analyzed by using fixed- and random-effects models under various genetic models.


RESULTS
A total of 277 (47.5%) and 306 (52.5%) patients were VPA nonresponsive and responsive, respectively. Unlike Chinese and Indian patients, Malay nonresponsive patients with idiopathic generalized epilepsy showed significant association, probably caused by the small sample size.


CONCLUSIONS
The cohort study and meta-analysis did not demonstrate an association between AED responsiveness and this polymorphism. Future studies with a larger sample size of Malays with idiopathic generalized epilepsy are suggested.
Pharmacogenomics Laboratory, Department of Pharmacology, University of Malaya, Kuala Lumpur, Malaysia. batoolsadat@yahoo.com
Batoul Sadat
BS
Haerian
Larry
L
Baum
Hui Jan
HJ
Tan
Patrick
P
Kwan
Azman Ali
AA
Raymond
Junji
J
Saruwatari
Kazuko
K
Nakagawa
Zahurin
Z
Mohamed
D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D000927:Anticonvulsants / Q000494:pharmacology*; D044466:Asian People / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006723:Hong Kong; D006801:Humans; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D011110:Polymorphism, Genetic; D014635:Valproic Acid / Q000494:pharmacology*; D055815:Young Adult
D000927:Anticonvulsants; D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; D014635:Valproic Acid