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 metabol ism and effects of omeprazole during short-term treatment. Aim: To investigate the relationship between CYP2C19 genotype and the effec ts of long-term omeprazole treatment. Material and methods: A total of 180 patients with acid related disorders w ere genotyped for wild type and mutated CYP2C19 alleles by allele-specific PCR amplification. Gastrin and chromogranin A were assessed by radioimmunoa ssays, and pepsinogen I and H. pylori serology were assessed by ELISA metho ds. Results: In 108 of the patients, who received a single dose of 20 mg omepra zole, 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 chr omogranin 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), respe ctively) compared to wild type/wild type (14.7 +/- 0.9 pM and 2.5 +/- 0.1 n M (n=52), respectively; both comparisons P=0.0001). In a single mutated/mut ated patient on long-term treatment, both gastrin and chromogranin A were h igh (88 pM and 13.7 nM, respectively). Serum pepsinogen I concentration was significantly lower in wild type/mutated (n=19) patients on long-term trea tment, compared with the corresponding wild type/wild type (n=49) group (14 7 +/- 19 mug/L vs. 193 +/- 12 mug/L, P=0.04). Conclusion: 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 co mpared with patients with two normal alleles. This indicates that changes i n gastric mucosal morphology during omeprazole treatment might be dependent upon the degree of the individual's capacity to metabolize omeprazole.