D-2 DOPAMINE-RECEPTOR ALLELES DO NOT INFLUENCE SEVERITY OF TOURETTES-SYNDROME - RESULTS FROM 4 LARGE KINDREDS

Objective: We investigated the recently proposed hypothesis that the A1 allele of the Taq I polymorphic system at the D-2 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 ties 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 ties, rated separately. We divided this sample (n=17, nine with TS and eight with chronic multiple ties) 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 2.8, the A1 homozygotes (n=2) 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.