PMID- 28884817
OWN - NLM
STAT- MEDLINE
DCOM- 20180719
LR  - 20180719
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 58
IP  - 1
DP  - 2018 Jan
TI  - Association Between CYP2C19*17 Alleles and pH Probe Testing Outcomes in Children 
      With Symptomatic Gastroesophageal Reflux.
PG  - 89-96
LID - 10.1002/jcph.977 [doi]
AB  - Esophageal pH monitoring remains a primary diagnostic tool for detecting 
      gastroesophageal reflux disease (GERD). GERD that is refractory to proton pump 
      inhibitor (PPI) medications may be related to CYP2C19 variants. Current PPI 
      dosing practices in children do not take into account CYP2C19 allelic variants, 
      which may lead to underdosing and subsequently to a misperception of PPI therapy 
      failure. We hypothesized that pH probe acid exposure outcomes associate with 
      CYP2C19*17 alleles among children with clinical concern for GERD. We identified a 
      retrospective cohort of 74 children (age range 0.71-17.1 years, mean 8.5, SD 4.6) 
      with stored endoscopic tissue samples and who had also undergone esophageal pH 
      testing while on PPI therapy. These individuals were genotyped for common CYP2C19 
      alleles and were dichotomized to either CYP2C19*17 allelic carriers without 
      corresponding loss of function alleles as cases vs controls. Associations between 
      pH probe acid exposure outcomes and CYP2C19*17 alleles were investigated. 
      Compared to controls, children who carry CYP2C19*17 alleles without corresponding 
      loss-of-function alleles demonstrated statistically significant longer times with 
      pH < 4 (76.46 vs 33.47 minutes, P = .03); and higher percent of time with pH < 
      4.0 (5.71 vs 2.67 minutes, P = .04). These findings remained statistically 
      significant using multiple-regression modeling with test duration, PPI dose, and 
      race as confounding variables. PPI therapy in children with *17 alleles may be 
      better optimized with CYP2C19 genotype-guided dosing prior to pH probe testing.
CI  - (c) 2017, The American College of Clinical Pharmacology.
FAU - Franciosi, James P
AU  - Franciosi JP
AD  - Division of Gastroenterology, Nemours Children's Hospital, Orlando, FL, USA.
FAU - Mougey, Edward B
AU  - Mougey EB
AD  - Center for Pharmacogenomics and Translational Research, Nemours Children's Health 
      System, Jacksonville, FL, USA.
FAU - Williams, Andre
AU  - Williams A
AD  - Center for Health Care Delivery Science, Nemours Children's Health System, 
      Jacksonville, FL, USA.
FAU - Gomez-Suarez, Roberto A
AU  - Gomez-Suarez RA
AD  - Division of Gastroenterology, Nemours Children's Hospital, Orlando, FL, USA.
FAU - Thomas, Cameron
AU  - Thomas C
AD  - Center for Pharmacogenomics and Translational Research, Nemours Children's Health 
      System, Jacksonville, FL, USA.
FAU - Creech, Christa L
AU  - Creech CL
AD  - Center for Pharmacogenomics and Translational Research, Nemours Children's Health 
      System, Jacksonville, FL, USA.
FAU - George, Katherine
AU  - George K
AD  - Center for Pharmacogenomics and Translational Research, Nemours Children's Health 
      System, Jacksonville, FL, USA.
FAU - Corao, Diana
AU  - Corao D
AD  - Department of Pathology, Alfred I., DuPont Hospital for Children, Wilmington, DE, 
      USA.
FAU - Lima, John J
AU  - Lima JJ
AD  - Center for Pharmacogenomics and Translational Research, Nemours Children's Health 
      System, Jacksonville, FL, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20170908
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Proton Pump Inhibitors)
RN  - EC 1.14.14.1 (CYP2C19 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alleles
MH  - Child
MH  - Child, Preschool
MH  - Cytochrome P-450 CYP2C19/*genetics
MH  - Esophageal pH Monitoring/methods
MH  - Female
MH  - Gastroesophageal Reflux/drug therapy/*genetics
MH  - Genotype
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Prospective Studies
MH  - Proton Pump Inhibitors/therapeutic use
MH  - Young Adult
OTO - NOTNLM
OT  - CYP2C19
OT  - GERD
OT  - children
OT  - proton pump inhibitor
EDAT- 2017/09/09 06:00
MHDA- 2018/07/20 06:00
CRDT- 2017/09/09 06:00
PHST- 2017/02/13 00:00 [received]
PHST- 2017/06/13 00:00 [accepted]
PHST- 2017/09/09 06:00 [pubmed]
PHST- 2018/07/20 06:00 [medline]
PHST- 2017/09/09 06:00 [entrez]
AID - 10.1002/jcph.977 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2018 Jan;58(1):89-96. doi: 10.1002/jcph.977. Epub 2017 Sep 8.