No major role of common SV2A variation for predisposition or levetiracetam response in epilepsy.

Abstract:

:Levetiracetam (LEV), a newer antiepileptic drug (AED) useful for several epilepsy syndromes, binds to SV2A. Identifying genetic variants that influence response to LEV may allow more tailored use of LEV. Obvious candidate genes are SV2A, SV2B and SV2C, which encode the only known binding site, synaptic vesicle protein 2 (SV2), with LEV binding to the SV2A isoform. SV2A is an essential protein as homozygous SV2A knockout mice appear normal at birth but fail to grow, experience severe seizures and die by 3 weeks. We addressed characterising AED response issues in pharmacogenetics and whether variation in these genes associates with response to LEV in two independent cohorts with epilepsy. We also investigated whether variation in these three genes associated with epilepsy predisposition in two larger cohorts of patients with various epilepsy phenotypes. Common genetic variation in SV2A, encoding the actual binding site of LEV, was fully represented in this study whereas SV2B and SV2C were not fully covered. None of the polymorphisms tested in SV2A, SV2B or SV2C influence LEV response or predisposition to epilepsy. We found no association between genetic variation in SV2A, SV2B or SV2C and response to LEV or epilepsy predisposition. We suggest this study design may be used in future pharmacogenetic work examining AED or LEV efficacy. However, different study designs would be needed to examine common variation with minor effect sizes, or rare variation, influencing AED or LEV response or epilepsy predisposition.

journal_name

Epilepsy Res

journal_title

Epilepsy research

authors

Lynch JM,Tate SK,Kinirons P,Weale ME,Cavalleri GL,Depondt C,Murphy K,O'Rourke D,Doherty CP,Shianna KV,Wood NW,Sander JW,Delanty N,Goldstein DB,Sisodiya SM

doi

10.1016/j.eplepsyres.2008.09.003

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

44-51

issue

1

eissn

0920-1211

issn

1872-6844

pii

S0920-1211(08)00259-3

journal_volume

83

pub_type

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