Reappraisal of the role of the DRD3 gene in essential tremor

Blair, Marcia A.; Ma, Shaochun; Phibbs, Fenna; Fang, John Y.; Cooper, Michael K.; Davis, Thomas L.; Hedera, Peter

doi:10.1016/j.parkreldis.2007.11.002

« Previous Next »Parkinsonism & Related Disorders
Volume 14, Issue 6 , Pages 471-475, August 2008

Reappraisal of the role of the DRD3 gene in essential tremor

Marcia A. Blair
- Department of Neurology, Vanderbilt University, TN, USA
Shaochun Ma
- Department of Neurology, Vanderbilt University, TN, USA
Fenna Phibbs
- Department of Neurology, Vanderbilt University, TN, USA
John Y. Fang
- Department of Neurology, Vanderbilt University, TN, USA
Michael K. Cooper
- Department of Neurology, Vanderbilt University, TN, USA
Thomas L. Davis
- Department of Neurology, Vanderbilt University, TN, USA
Peter Hedera
- Department of Neurology, Vanderbilt University, TN, USA
- Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA
- Corresponding author. Department of Neurology, Vanderbilt University, 465 21st Avenue South, 6140 MRB III, Nashville, TN 37232-8552, USA. Tel.: +1 615 936 3920; fax: +1 615 322 5517.

Received 27 September 2007; received in revised form 21 November 2007; accepted 25 November 2007.

Abstract

Objectives

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.