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ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression
- Source :
- The Pharmacogenomics Journal. 15:332-339
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- The hypothesis that allelic variation in the multidrug resistance-1 (MDR1 or ABCB1) gene encoding the P-glycoprotein (P-gp) blood-brain barrier efflux pump is associated with remission and side effects was tested in chronic major depression patients treated with P-gp substrates. In 83 patients from the REVAMP trial, frequency of and time to remission as well as side effects was tested among genotype groups at 6 ABCB1 single nucleotide polymorphisms (SNPs). These six SNPs are significantly associated with remission and time to remission, with minor allele carriers on rs2235040 and rs9282564 attaining statistical significance after controlling for the other ABCB1 SNPs. The six ABCB1 SNPs are also significantly associated with the average side effects. However, here common homozygotes on rs2235040 and rs9282564 demonstrated significantly higher side effects after controlling for the effects of the other ABCB1 SNPs. These findings confirm and extend previous observations that minor alleles of two ABCB1 SNPs predict remission to treatment with substrates and demonstrate that common homozygotes on these SNPs experience greater side effects. Results point to the potential importance of ABCB1 variation for personalized medicine approaches to treating depression.
- Subjects :
- Adult
Male
Oncology
medicine.medical_specialty
ATP Binding Cassette Transporter, Subfamily B
Genotype
Single-nucleotide polymorphism
Kaplan-Meier Estimate
Biology
Polymorphism, Single Nucleotide
White People
Sertraline
Statistical significance
Internal medicine
Genetics
medicine
Humans
ATP Binding Cassette Transporter, Subfamily B, Member 1
Allele
Gene
Alleles
Depression (differential diagnoses)
Pharmacology
Depressive Disorder, Major
Dose-Response Relationship, Drug
business.industry
Middle Aged
Antidepressive Agents
Minor allele frequency
Treatment Outcome
Chronic Disease
Molecular Medicine
Female
Personalized medicine
business
Subjects
Details
- ISSN :
- 14731150 and 1470269X
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- The Pharmacogenomics Journal
- Accession number :
- edsair.doi.dedup.....f98bcae01a46f83f10c02a82c4c710c2
- Full Text :
- https://doi.org/10.1038/tpj.2014.72