Effect of CYP2C19 polymorphism on serum levels of vitamin B12 in patients on long-term omeprazole treatment

Abstract

Background: The S-mephenytoin hydroxylase is a polymorphic cytochrome P450 (CYP) enzyme, identified as CYP2C19, which catalyses the metabolism of omeprazole and some other drugs. Aim: To determine whether long-term treatment with omeprazole affects serum vitamin B12 levels, and if so to what extent it depends on CYP2C19 activity. Methods: Serum vitamin B12 levels (pmol/L) were assessed in 179 patients. Genotyping for wild-type (wt) and mutated (mut) CYP2C19 alleles was performed by allele-specific PCR amplification. Results: One-hundred and eleven of the patients received one dose of 20 mg omeprazole..No difference in B12 levels were found between heterozygous (wt/mut) (n = 23) and homozygous (wt/wt) (n = 85) patients (mean ± s.d., 350 ± 82 vs, 315 ± 87 pmol/L, respectively). Three patients were mut/mut, with serum vitamin B12 levels of 303 ± 50 pmol/L. In the 68 patients on long-term (> 1 year) therapy with 20 mg omeprazole daily, serum vitamin B12 levels were lower in the heterozygous (wt/mut) (n = 19) compared to homozygous wt/wt (n = 49) (246 ± 71 vs. 305 ± 98 pmol/L, P = 0.01, respectively). In one patient (mut/mut) who was studied both after a single dose and after long-term (15 months) treatment with omeprazole, serum vitamin B12 decreased from 360 to 178 pmol/L. In the wt/mut, but not in the wt/wt group, serum vitamin B12 levels were significantly lower in patients on long-term therapy compared with those receiving one dose (246 ± 71 vs. 350 ± 82 pmol/L, P < 0.0001, respectively). Conclusions: CYP2C19 polymorphism significantly affected serum vitamin B12 levels in patients on long-term therapy with omeprazole. In the future, genotyping of CYP2C19 may be useful for patients in need of long-term treatment with omeprazole or other proton pump inhibitors.