title: Genetic variation and the risk of haloperidol-related parkinsonism in elderly patients: a candidate gene approach.
abstract: Factors that influence the variation in occurrence of antipsychotic-related parkinsonism in elderly have not been well elucidated. The aim of this study was to investigate whether previous identified and studied genetic polymorphisms at DRD2, ANKK1, DRD3, HTR2A, HTR2C, RGS2, COMT, and BDNF genes are associated with antipsychotic-related parkinsonism in elderly patients.This cross-sectional study included 150 inpatients aged 65 years and older who were treated with haloperidol. Parkinsonism assessed by the Simpson Angus Scale was present in 46% of the included patients. The investigated predictors were polymorphisms in DRD2 (141CIns/Del and C957T), ANNK1 (TaqIA), DRD3 (Ser9Gly), HTR2A (-1438G>A and His452Tyr), HTR2C (Cys23Ser and -759C/T), RGS2 (+2971C>G), COMT (G158A), and BDNF (Val66Met). Frequencies of the -759 T allele of the HTR2C gene and the 158A allele of the COMT gene were significantly higher in patients without antipsychotic-induced parkinsonism (AIP) (nominal P = 0.03 and P = 0.02, respectively). -759 T allele carriership in females was associated with a lower risk of AIP (adjusted odds ratio, 0.31; 95% confidence interval, 0.11-0.85). The decrease in risk of AIP in carriers of the COMT 158A allele did not reach statistical significance. No significant associations were found between AIP and the remaining selected polymorphisms.Although validation is needed, this study suggests that carriership of the -759 T allele of the HTR2C gene in females may be protective against development of parkinsonism in elderly patients during treatment with haloperidol.
authors.affiliation: Department of Geriatrics and Expertise Center Pharmacotherapy in Old Persons, University Medical Center Utrecht, Utrecht, the Netherlands. w.knol@umcutrecht.nl
authors.forename: Wilma
authors.initials: W
authors.lastname: Knol
authors.forename: Rob J
authors.initials: RJ
authors.lastname: van Marum
authors.forename: Paul A F
authors.initials: PA
authors.lastname: Jansen
authors.forename: Eric
authors.initials: E
authors.lastname: Strengman
authors.forename: Asmar F Y
authors.initials: AF
authors.lastname: Al Hadithy
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
authors.forename: Alfred F A M
authors.initials: AF
authors.lastname: Schobben
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
authors.forename: Toine C G
authors.initials: TC
authors.lastname: Egberts
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006220:Haloperidol / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D011110:Polymorphism, Genetic; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D012306:Risk; D012737:Sex Factors
chemical_list: D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D006220:Haloperidol