DRD3 variant and risk of essential tremor

Abstract

Linkage analysis studies in Icelandic and North American families have identified three genetic loci where the causative essential tremor (ET) gene could be located: chromosome 3q13 (ETM1), 2p22-p25 (ETM2), and 6p23.1–3 The A265G variant in the HS1-BP3 gene has been shown to associate with familial ET.4 ETM2 has previously been linked to ET in our population.5 Though the HS1-BP3 variant was not found in our patients with ET,4 the possible association with other variants of HS1-BP3 or other genes has not been excluded. The dopamine D3 receptor ( DRD3 ) gene is located near the ETM1 locus. Recently, a functional DRD3 variant (Ser9Gly) was found to be associated with risk and age at onset of ET in American and French populations.6 The Gly-9 (G) allele cosegregated with ET in 23 families and Gly-9 homozygotes appeared to have more severe ET symptoms.6 Furthermore, in vitro studies showed that dopamine-mediated cAMP response was increased and mitogen-associated protein kinase (MAPK) was prolonged with the G allele.6 The biologic plausibility of the DRD3 Ser9Gly variant, the concordance of the clinical …