D2 Dopamine Receptor Alleles Do Not Influence Severity of Tourette's Syndrome: Results From Four Large Kindreds
Abstract
OBJECTIVE: We investigated the recently proposed hypothesis that the A1 allele of the Taq I polymorphic system at the D2 dopamine receptor gene (DRD2) influences the severity of Tourette's syndrome (TS). We have previously demonstrated that DRD2 is not linked to TS, establishing that it cannot be the major locus determining the susceptibility to develop TS. METHOD: We studied alleles at the DRD2 A system in patients with TS or chronic multiple tics in four extended kindreds segregating TS. If this allelic system at DRD2 is associated with severity of TS, then among affected family members, those with the A1 allele should have more severe disease than those without it. Severity of disease was compared in affected members of the kindreds with A1 alleles and in those without A1 alleles. RESULTS: We evaluated disease severity in two ways. First, we evaluated 17 individuals from two families using a derivative of the Yale Global Tic Severity Scale composed of subscales concerning number, frequency, and severity of motor and phonic tics, rated separately. We divided this sample (n = 17, nine with TS and eight with chronic multiple tics) by genotype at the A1/A2 system. The heterozygotes (n = 7) had an average severity score of 11.3; the A2 homozygotes had an average severity score of 14.2. (There were no A1 homozygotes.) Second, we evaluated 47 individuals from two different families (all with TS) using the TS symptomatology evaluation. We compared severity scores for these individuals by genotype at the A1/A2 system. The heterozygotes (n = 24) had a mean severity score of 3.0, and the A2 homozygotes (N = 21) had a mean severity score of 3.7. CONCLUSION: Our data do not support alleles at the A system of DRD2 as a factor associated with severity of TS.
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Variants in the DA receptor gene DRD2 have been associated with genetic risk for TS, but this finding is not consistent.
“Variants in the DA receptor gene DRD2 have also been associated with genetic risk for TS [626-628], but this finding is not consistent [629-633].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [632]
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- Authors
- Gelernter, J.
- Affiliations
- Veterans Health Administration (US)
- Corresponding author
- Gelernter, Joel
- ORCID
- Gelernter, Joel
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 1994-04-01
- Volume
- 51
- Issue
- 4
- Pages
- 397
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2094055942
- Cited by
- 41
- References
- 27
- Citations by year
- 2026: 1 · 2022: 2 · 2019: 1 · 2017: 1 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (NIMH MH00931, NIMH MH-00508, NIMH MH30929)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- Tourette syndrome, dopamine D2 receptor, DRD2 gene, TaqI polymorphism, A1 allele, disease severity, tic severity, family segregation, genotype-phenotype correlation
- MeSH terms
- Alleles, Tourette Syndrome, Heterozygote, Homozygote, Humans, Genetic Linkage, Severity of Illness Index, Receptors, Dopamine D2
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