<i>CYP2C19</i> Polymorphism and Risk for Essential Tremor

Abstract

Many patients with essential tremor (ET) develop acute adverse effects to primidone. We investigated the association between <i>CYP2C19</i> polymorphism (possibly related to primidone metabolism) and the risk for developing essential ET and acute adverse effects to primidone. Leukocytary DNA from 200 ET patients and 300 healthy controls was studied for the genotype <i>CYP2C19 </i>and the occurrence of <i>CYP2C19</i> allelic variants by using allele-specific PCR amplification and <i>Sma</i> I and <i>Bam</i>H I RFLP analyses. The frequencies of the genotype <i>CYP2C19</i>*<i>1/CYP2C19</i>*<i>2 </i>and of the allelic variant <i>CYP2C19</i>*<i>2</i> were significantly higher in ET patients than in controls. The mean age at onset of ET did not differ significantly between patients with genotypes <i>CYP2C19</i>*<i>1/CYP2C19</i>*<i>2</i>and<i>CYP2C19</i>*<i>1/CYP2C19</i>*<i>1</i>. The frequencies of the genotype <i>CYP2C19</i>*<i>1/CYP2C19</i>*<i>2</i> and the allelic variant <i>CYP2C19</i>*<i>2 </i>were similar in ET patients who developed acute adverse effects to primidone, in those who tolerated primidone and in controls; the frequencies were also similar in patients with head, voice, tongue and chin tremor compared with controls. These results suggest that heterozygosis <i>CYP2C19</i>*<i>1/CYP2C19</i>*<i>2</i> is associated with the risk for ET, but not with the age at onset of ET, the presentation of acute side effects of primidone, or the existence of head, voice, tongue or chin tremor.