CYP2C19 pharmacogenetics in the clinical use of proton-pump inhibitors for gastro-oesophageal reflux disease: variant alleles predict gastric acid suppression, but not oesophageal acid exposure or reflux symptoms.
BACKGROUND
The rate of metabolic inactivation of proton-pump inhibitors is determined by polymorphisms of CYP2C19. It is not known if CYP2C19 variant alleles affect responses to proton-pump inhibitor therapy in gastro-oesophageal reflux disease (GERD).


OBJECTIVE
To determine if the CYP2C19 genotype is associated with clinical effectiveness of proton-pump inhibitors during GERD therapy.


METHODS
GERD patients undergoing ambulatory gastric and oesophageal pH monitoring were genotyped for CYP2C19 polymorphisms.


RESULTS
Sixty subjects were enrolled. Forty-four subjects had two wild-type alleles, 15 had one variant, and one had two variant CYP2C19 alleles. The presence of a variant allele was significantly associated with a lower odds of gastric acid breakthrough during proton-pump inhibitor therapy [odds ratio 5.14, 95% confidence interval (CI) 1.17-22.61]. The presence of a variant allele was not associated with a lower odds of significant oesophageal acid exposure (odds ratio 2.50, 95% CI 0.60-10.52), or the occurrence of symptoms (incidence rate ratio 1.06, 95% CI 0.54-2.06).


CONCLUSIONS
These results indicate that factors other than gastric acid secretion are important determinants of reflux in GERD patients. This suggests that CYP2C19 genotype testing will not be useful in proton-pump inhibitor therapy of GERD, except perhaps in identifying patients at risk for hypochlorhydria and consequent hypergastrinemia.
Egan
L J
LJ
Clinical Pharmacology Unit, Division of Gastroenterology and Hepatology and Division of Biostatistics, Mayo Clinic, Rochester, Minnesota 55905, USA. egan.laurence@mayo.edu
Myhre
G M
GM
Mays
D C
DC
Dierkhising
R A
RA
Kammer
P P
PP
Murray
J A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D054328:Proton Pump Inhibitors; D012307:Risk Factors
D054328:Proton Pump Inhibitors; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19