Genetic polymorphism of dopamine D2 receptors in Parkinson's disease and interactions with cigarette smoking and MAO-B intron 13 polymorphism.
Genetic polymorphisms of dopamine D2 receptors (DRD2) may be susceptibility factors for Parkinson's disease due to their influence on dopamine response and association with cigarette smoking, which is inversely related to risk of Parkinson's disease. Relations of TaqIA and TaqIB DRD2 genotypes with Parkinson's disease were investigated and tested for interactive effects with smoking and the monoamine oxidase B (MAO-B) intron 13 polymorphism previously found to be related to smoking. Study subjects were 152 cases of idiopathic Parkinson's disease and 231 controls. The smoking history of all genotyped subjects was known. Subjects of genotype B12 were more frequent among cases than controls (27% and 23.8%, respectively), and were more frequent among "ever smokers" than "never smokers", among controls (27.8% and 17.2%, respectively), although these associations were not statistically significant. Neither TaqIA or TaqIB genotypes modified the inverse relation of smoking and Parkinson's disease. When genotypes for DRD2 were considered in combination with genotypes for intron 13 of MAO-B, genotype combinations with high risk of Parkinson's disease were found; although the MAO-B/DRD2 interaction did not reach statistical significance after Bonferroni correction for multiple comparisons, these results are suggestive of a possible synergism between MAOB and DRD2 genes with respect to Parkinson's disease.
Costa-Mallen
P
P
Department of Environmental Health, University of Washington School of Public Health and Community Medicine, 4225 Roosevelt Way NE 100, Seattle, WA 98105-6099, USA. cstpla@u.washington.edu
Costa
L G
LG
Smith-Weller
T
T
Franklin
G M
GM
Swanson
P D
PD
Checkoway
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D010300:Parkinson Disease / Q000473:pathology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012907:Smoking / Q000235:genetics*
D017448:Receptors, Dopamine D2; D008995:Monoamine Oxidase