Omeprazole and CYP2C19 polymorphism: effects of long-term treatment on gastrin, pepsinogen I, and chromogranin A in patients with acid related disorders.
BACKGROUND
The polymorphic enzyme CYP2C19 is of importance for the metabolism and effects of omeprazole during short-term treatment.


OBJECTIVE
To investigate the relationship between CYP2C19 genotype and the effects of long-term omeprazole treatment.


METHODS
A total of 180 patients with acid related disorders were genotyped for wild type and mutated CYP2C19 alleles by allele-specific PCR amplification. Gastrin and chromogranin A were assessed by radioimmunoassays, and pepsinogen I and H. pylori serology were assessed by ELISA methods.


RESULTS
In 108 of the patients, who received a single dose of 20 mg omeprazole, there was no difference in gastrin and chromogranin A concentrations between the three CYP2C19 genotypes. In 72 patients on long-term treatment (> 1 year) with 20 mg omeprazole daily, serum gastrin as well as plasma chromogranin A concentrations (mean +/- s.e.) were both about threefold higher in the wild type/mutated (52.1 +/- 7.6 pM and 7.3 +/- 1.3 nM (n=19), respectively) compared to wild type/wild type (14. 7 +/- 0.9 pM and 2.5 +/- 0.1 nM (n=52), respectively; both comparisons P=0.0001). In a single mutated/mutated patient on long-term treatment, both gastrin and chromogranin A were high (88 pM and 13.7 nM, respectively). Serum pepsinogen I concentration was significantly lower in wild type/mutated (n=19) patients on long-term treatment, compared with the corresponding wild type/wild type (n=49) group (147 +/- 19 microg/L vs. 193 +/- 12 microg/L, P=0. 04).


CONCLUSIONS
Patients with one (and probably also with two) mutated CYP2C19 allele(s) on long-term treatment with omeprazole had significantly affected serum gastrin and pepsinogen I and plasma chromogranin A concentrations compared with patients with two normal alleles. This indicates that changes in gastric mucosal morphology during omeprazole treatment might be dependent upon the degree of the individual's capacity to metabolize omeprazole.
Sagar
M
M
Center of Gastroenterology, Departments of Surgery and Medicine, Clinical Research Center, Sweden.
Bertilsson
L
L
Stridsberg
M
M
Kjellin
A
A
Mârdh
S
S
Seensalu
R
R
D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases; D014408:Biomarkers, Tumor / Q000097:blood*; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood*; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000097:blood*; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D005838:Genotype; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000627:therapeutic use*; D020116:Pepsinogen A / Q000097:blood*; D010437:Peptic Ulcer / Q000097:blood / Q000188:drug therapy; D011110:Polymorphism, Genetic; D011863:Radioimmunoassay
D000897:Anti-Ulcer Agents; D014408:Biomarkers, Tumor; C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D005755:Gastrins; D020116:Pepsinogen A; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole