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


OBJECTIVE
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.
Sagar
M
M
Center of Gastroenterology, Departments of Surgery and Medicine, Clinical Research Center, Stockholm, Sweden.
Janczewska
I
I
Ljungdahl
A
A
Bertilsson
L
L
Seensalu
R
R
D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004941:Esophagitis / Q000188:drug therapy / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009853:Omeprazole / Q000494:pharmacology* / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000188:drug therapy / Q000201:enzymology; D011110:Polymorphism, Genetic; D014805:Vitamin B 12 / Q000097:blood*
D000897:Anti-Ulcer Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; 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; D014805:Vitamin B 12