Genetic polymorphism of the angiotensin converting enzyme and L-dopa-induced adverse effects in Parkinson's disease.
There was increasing evidence suggesting that angiotensin I-converting enzyme may play an important role in the pathogenesis of PD. Our former study has shown that angiotensin I-converting enzyme gene (ACE) may confer a susceptibility for the risk of Parkinson's disease (PD). Meanwhile, recent studies have emphasized that genetic factors may involve in the occurrence of the adverse effects of chronic L-dopa therapy in PD patients. This study was designed to assess whether genetic polymorphism of the ACE could be a predictor of L-dopa-induced adverse effects in PD. There were 251 patients included in this study and their mean age at onset of disease was 63.3+/-11.4 years. The duration of disease and the treatment with L-dopa was 6.3+/-5.1 and 5.0+/-4.3 years, respectively. The frequency of the homozygote ACE-II genotype of the ACE in PD patients with L-dopa-induced psychosis was significantly higher than that in PD patients without the adverse effect (63.3% vs 43.0%; chi(2)=6.347, OR=1.435, 95%CI=1.105-1.864, p=0.012). However, the ACE polymorphism was not associated with the risk to develop dyskinesia or motor fluctuation induced by L-dopa. Furthermore, a logistic regression analysis confirmed that the ACE-II genotype was an independent risk factor for L-dopa-induced psychosis in PD patients (OR=2.542, p=0.012). In conclusion, results of the study showed that ACE-II genotype might confer a primary predictor for the occurrence of psychosis in L-dopa-treated PD.
Lin
Juei-Jueng
JJ
Department of Neurology, Chushang Show-Chwan Hospital, Nantou, 557, Taiwan. jjlinn@tcts.seed.net.tw
Yueh
Kuo-Chu
KC
Lin
Shinn-Zong
SZ
Harn
Horng-Jyh
HJ
Liu
Jung-Tung
JT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006720:Homozygote; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011605:Psychoses, Substance-Induced / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
D000978:Antiparkinson Agents; D007980:Levodopa; D007703:Peptidyl-Dipeptidase A