Reappraisal of the role of the DRD3 gene in essential tremor.
OBJECTIVE
Analyze the distribution of polymorphism in the dopamine receptor D3 (DRD3) gene, which was previously reported as a susceptibility risk for essential tremor (ET), in a large cohort of ET.


METHODS
The role of 312G>A DRD3 polymorphism was analyzed using linkage analysis, association study and transmission disequilibrium test in a group of 433 ET patients, and two unrelated control groups with 121 and 151 individuals.


RESULTS
Allelic frequencies of glycine and serine forms of the DRD3 gene did not differ between patients and both control groups, and were in Hardy-Weinberg equilibrium. Linkage analysis identified obligatory recombinants in every large pedigree, even in those with relatively high frequency of glycine allele, thus excluding the linkage to this locus. Both alleles were transmitted with an equal likelihood to affected offspring. We also failed to replicate the relationship between glycine homozygosity and an earlier age of onset or more severe tremor course.


CONCLUSIONS
Our comprehensive genetic analysis in a large ET cohort strongly argues against the role of the DRD3 gene in ET pathogenesis.
Blair
Marcia A
MA
Department of Neurology, Vanderbilt University, TN, USA.
Ma
Shaochun
S
Phibbs
Fenna
F
Fang
John Y
JY
Cooper
Michael K
MK
Davis
Thomas L
TL
Hedera
Peter
P
D000368:Aged; D000483:Alleles; D020329:Essential Tremor / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D005998:Glycine / Q000502:physiology; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D012694:Serine / Q000502:physiology
C493593:DRD3 protein, human; D050637:Receptors, Dopamine D3; D012694:Serine; D005998:Glycine