PMID- 29985178
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20190729
IS  - 1473-6578 (Electronic)
IS  - 0951-7367 (Linking)
VI  - 31
IP  - 5
DP  - 2018 Sep
TI  - Clozapine pharmacogenomics: a review of efficacy, pharmacokinetics, and 
      agranulocytosis.
PG  - 403-408
LID - 10.1097/YCO.0000000000000440 [doi]
AB  - PURPOSE OF REVIEW: To examine recent literature regarding the pharmacogenomics of 
      clozapine (CLZ) efficacy, pharmacokinetics, and agranulocytosis. RECENT FINDINGS: 
      Several genetic loci (FKBP5, NR3C1, BDNF, NTRK2) along the hypothalamic pituitary 
      adrenal axis have been investigated as targets for CLZ response. Homozygous 
      FKBP5-rs1360780, homozygous NTRK2-rs1778929, and homozygous NTRK2-rs10465180 
      conferred significant risks for CLZ nonresponse - 2.11x risk [95% confidence 
      interval (CI) 1.22-3.64], 1.7x risk (95% CI 1.13-2.59), and 2.15x risk (95% CI 
      1.3-3.55), respectively. BDNF and NR3C1 had no significant associations with CLZ 
      response. Candidate genes within neurotransmitter pathways continue to be 
      explored including dopaminergic (DRD1-4, COMT) and glutamatergic pathways 
      (GRIN2B, SLC1A2, SLC6A9, GRIA1, GAD1). Despite promising trending data, no 
      significant associations between CLZ response and glutamatergic system variants 
      have been found. Synergistic effect of catecholamine O-methyltransferase (COMT) 
      Met and dopamine receptor-4 (DRD4) single 120 bp duplicate associated with 
      improved CLZ response odds ratio (OR) 0.15 (95% CI 0.03-0.62) while COMT Val/Val 
      confer a risk of CLZ nonresponse OR 4.34 (95% CI 0.98-23.9). Diagnostic 
      performance testing continues through human leukocyte antigen (HLA) and other 
      genetic loci but have yet to find statistically or clinically meaningful results. 
      SUMMARY: Current landscape of pharmacogenomic research in CLZ continues to be 
      limited by small sample sizes and low power. However, many promising candidate 
      genes have been discovered and should be further investigated with larger 
      cohorts.
FAU - Li, Kevin J
AU  - Li KJ
AD  - Veterans Affairs (VA) Boston Healthcare System, Boston.
AD  - Harvard South Shore Psychiatry Residency Training Program, Brockton.
AD  - Harvard Medical School, Boston, Massachusetts, USA.
FAU - Solomon, Haley V
AU  - Solomon HV
AD  - Veterans Affairs (VA) Boston Healthcare System, Boston.
AD  - Harvard South Shore Psychiatry Residency Training Program, Brockton.
AD  - Harvard Medical School, Boston, Massachusetts, USA.
FAU - DeLisi, Lynn E
AU  - DeLisi LE
AD  - Veterans Affairs (VA) Boston Healthcare System, Boston.
AD  - Harvard South Shore Psychiatry Residency Training Program, Brockton.
AD  - Harvard Medical School, Boston, Massachusetts, USA.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Curr Opin Psychiatry
JT  - Current opinion in psychiatry
JID - 8809880
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Glycine Plasma Membrane Transport Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NR3C1 protein, human)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (SLC6A9 protein, human)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
RN  - EC 5.2.1.- (Tacrolimus Binding Proteins)
RN  - EC 5.2.1.8 (tacrolimus binding protein 5)
RN  - J60AR2IKIC (Clozapine)
MH  - Agranulocytosis/*chemically induced
MH  - Antipsychotic Agents/adverse effects/*therapeutic use
MH  - Clozapine/adverse effects/*therapeutic use
MH  - Glycine Plasma Membrane Transport Proteins/genetics
MH  - Humans
MH  - Hypothalamo-Hypophyseal System/physiology
MH  - Membrane Glycoproteins/genetics
MH  - Pharmacogenetics
MH  - Pituitary-Adrenal System/physiology
MH  - Receptor, trkB/genetics
MH  - Receptors, Glucocorticoid/genetics
MH  - Schizophrenia/*drug therapy/genetics
MH  - Tacrolimus Binding Proteins/genetics
EDAT- 2018/07/10 06:00
MHDA- 2019/07/30 06:00
CRDT- 2018/07/10 06:00
PHST- 2018/07/10 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2018/07/10 06:00 [entrez]
AID - 10.1097/YCO.0000000000000440 [doi]
PST - ppublish
SO  - Curr Opin Psychiatry. 2018 Sep;31(5):403-408. doi: 10.1097/YCO.0000000000000440.