Dopamine receptor D3 gene and essential tremor in large series of German, Danish and French patients

Abstract

The genetic causes of essential tremor (ET) seem to be heterogeneous. Recently, ET has been found associated with a functional variant (Ser9Gly) of the dopamine D 3 receptor (DRD3), located in the ETM1 locus on chromosome 3q13.3 described for the first time in 1997. We examined this variant in three different populations from Germany, Denmark and France. We undertook an association study of the Ser9Gly variant in 202 cases with a familial history from unrelated families with ET, 97 cases with isolated non-familial ET and 528 healthy controls. In addition, linkage and segregation analyses were carried out in 22 ET families. The distribution of genotypes and allele frequencies showed no significant differences in the whole sample and in a subanalysis of familial and sporadic cases. Age at onset of tremor, tremor duration and tremor severity did not show an association with the genotype. In addition, the DRD3 variant was not found linked to the disease in a subset of informative ET families. We did not find a significant association of the DRD3 variant with ET nor linkage to the DRD3 receptor in German, Danish and French ET patients and families, suggesting that it is unlikely to be a causal factor for ET.

Gamma-aminobutyric acid (GABA) receptor rho (GABRR) polymorphisms and risk for essential tremor

“…[4]). Although a metaanalysis on dopaminergic receptor D 3 (DRD 3 ) gene polymorphism suggested an association between this polymorphism and the risk for ET [13], another study involving a large series of patients did not support this association [24]. Several recent reports suggested the association of the LINGO1 rs9652490 polymorphism with the risk of developing ET [7,38,[41][42][43][44].…”

LINGO1 polymorphisms are associated with essential tremor in Europeans

“…Several variants in different candidate genes were proposed to increase the risk of ET 18, 19. However, replication studies showed inconsistent results 20–23. Very recently, the first genome‐wide association study in ET revealed two intronic sequence variants (rs9652490 and rs11856808) to be associated with ET in the leucine‐rich repeat (LRR) and immunoglobulin domain containing, Nogo receptor‐interacting protein gene 1 ( LINGO1 ; OMIM: 609791) 24.…”

Key Issues in Essential Tremor Genetics Research: Where Are We Now and How Can We Move Forward?

“…Within ETM1, the dopamine D3 receptor (DRD3) gene ( DRD3 ) 312A→G variant is implicated in small, French ET families and in a case–control analysis of US subjects: DRD3 genotype was associated with age of onset and disease severity in these samples;65 an independent study of Spanish subjects also observed an association with both ET risk and ET age of onset 66. In contrast to these reports, replication studies in Asian, Latvian, German, French, Danish, Italian, and at least two independent US ET cohorts did not observe an association between DRD3 variants and ET risk or ET age of onset,39,64,67–70 or linkage with DRD3 in ET families 67, 69…”