OCT1 polymorphism is associated with response and survival time in anti-Parkinsonian drug users.
Substrates for the Organic Cation Transporter 1, encoded by the SLC22A1 gene, are metformin, amantadine, pramipexole, and, possibly, levodopa. Recently, we identified that the rs622342 A > C polymorphism is associated with the HbA1c lowering effect in metformin users. In the Rotterdam Study, we associated this polymorphism with higher prescribed doses of all anti-Parkinsonian drugs. Between the first and fifth prescriptions for levodopa, for each minor rs622342 C allele, the prescribed doses were 0.34 defined daily dose higher (95% CI 0.064, 0.62; p=0.017). The mortality ratio after start of levodopa therapy was 1.47 times higher (95% CI 1.01, 2.13; p=0.045).
Becker
Matthijs L
ML
Department of Epidemiology, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
Visser
Loes E
LE
van Schaik
Ron H N
RH
Hofman
Albert
A
Uitterlinden
André G
AG
Stricker
Bruno H Ch
BH
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D027702:Organic Cation Transporter 1 / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D016019:Survival Analysis
D000978:Antiparkinson Agents; D027702:Organic Cation Transporter 1; D007980:Levodopa