Lack of allelic association of dopamine D4 receptor gene polymorphisms with Parkinson's disease in a Chinese population

Parkinson's disease (PD) is a neurodegenerative disease caused by a multitu de of environmental, neurochemical, and genetic factors. The gene for human dopamine D4 receptor (DRD4) has been considered as a plausible candidate f or the pathogenesis of PD. Different dopamine D4 receptor allelic forms hav e variable affinity toward certain neuroleptics such as clozapine, suggesti ng a role for dopamine D4 receptors in neurologic disorders. To test the hy pothesis that the DRD4 polymorphism is associated with the susceptibility t o Parkinson's disease, we have examined differences in allele frequencies o f different DRD4 polymorphisms in 101 Chinese patients with PD and in 105 a ge-matched control subjects in Hong Kong. The DRD4 gene was analyzed by a n on-radioactive polymerase chain reaction-based Southern hybridization with chemiluminescence detection. The number of polymorphic 48 base pair tandem repeats in exon 3 was identified in each study subject. The DRD4 alleles wi th high frequencies in the control subjects are 4-repeat allele (72.4%), 2- repeat allele (21.4%), and 7-repeat allele (3.8%) which accounted for over 97% of the total alleles in the elderly Chinese population. The most preval ent genotype in the control subjects is the 4/4 (47.6%), followed by 4/2 (3 8.6), 4/7 (7.6%), and 2/2 (3.0%). None of the variable number tandem repeat polymorphism showed evidence for genetic association with Parkinson's dise ase.