ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression.
A RayL TennakoonJ KellerJ E SarginsonH S RyanG M MurphyLaura C LazzeroniM H TrivediJ H KocsisC DeBattistaA F SchatzbergPublished in: The pharmacogenomics journal (2014)
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.
Keyphrases
- genome wide
- blood brain barrier
- disease activity
- ulcerative colitis
- genome wide association
- dna methylation
- depressive symptoms
- end stage renal disease
- multidrug resistant
- rheumatoid arthritis
- ejection fraction
- systemic lupus erythematosus
- chronic kidney disease
- gene expression
- copy number
- prognostic factors
- study protocol
- cerebral ischemia
- open label
- brain injury
- physical activity
- phase ii
- human health
- genome wide identification