CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls in elderly people.
OBJECTIVE
The objective of this study is to investigate the association between CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls.


METHODS
Multivariate logistic regression was performed in an existing database in order to study the association between falls history and CYP2D6*4, CYP3A5*3, ABCB1 3435T polymorphisms in patients using fall-risk-increasing CYP2D6, CYP3A5 and P-glycoprotein (gene product of ABCB1) substrates.


RESULTS
No statistically significant increased fall risk was found in 'poor metabolizers' compared to 'extensive' and 'intermediate metabolizers' using fall-risk-increasing CYP2D6 substrates (Odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.2-25.0), CYP3A5 substrates (OR = 0.9; 95% CI 0.2-3.3) and P-glycoprotein substrates (OR = 2.1; 95% CI 0.2-17.2).


CONCLUSIONS
The hypothesis that 'poor metabolizers' have an increased fall risk was not confirmed. A larger study population is needed to confirm the potential association that was seen between CYP2D6*4 and ABCB1 3435T polymorphisms and drug-related falls.
Blonk
Maren I
MI
Department of Hospital Pharmacy, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. miblonk8@xs4all.nl
van der Velde
Nathalie
N
van den Bemt
Patricia M L A
PM
van Schaik
Ron H N
RH
van der Cammen
Tischa J M
TJ
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000058:Accidental Falls / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D010599:Pharmacokinetics; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D013223:Statistics as Topic
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C510164:CYP3A5 protein, human; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A