Effect of MDR1 C3435T polymorphism on cure rates of Helicobacter pylori infection by triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP 2C19 genotypes and 23S rRNA genotypes of H. pylori.
BACKGROUND
Polymorphism in MDR1 is associated with variation in the plasma level of a proton pump inhibitor.


OBJECTIVE
To investigate whether MDR1 polymorphism is associated with eradication rates of Helicobacter pylori by a triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP2C19 genotype status and bacterial susceptibility to clarithromycin.


METHODS
A total of 313 patients infected with H. pylori completed the treatment with lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week. MDR1 C3435T polymorphism and CYP2C19 genotypes of patients and sensitivity of H. pylori to clarithromycin were determined.


RESULTS
Logistic regression analysis revealed that the MDR1 polymorphism as well as CYP2C19 genotypes of patients and clarithromycin-resistance of H. pylori were significantly associated with successful eradication. Eradication rates for H. pylori were 82% (83/101: 95% CI = 73-89), 81% (112/139: CI = 73-87), and 67% (44/73: CI = 48-72) in patients with the MDR1 3435 C/C, C/T and T/T genotype, respectively (P = 0.001).


CONCLUSIONS
Polymorphism of MDR1 is one of the determinants of successful eradication of H. pylori by the triple therapy with lansoprazole, amoxicillin and clarithromycin, together with CYP2C19 genotype and bacterial susceptibility to clarithromycin.
Furuta
T
T
Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan. furuta@hama-med.ac.jp
Sugimoto
M
M
Shirai
N
N
Matsushita
F
F
Nakajima
H
H
Kumagai
J
J
Senoo
K
K
Kodaira
C
C
Nishino
M
M
Yamade
M
M
Ikuma
M
M
Watanabe
H
H
Umemura
K
K
Ishizaki
T
T
Hishida
A
A
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D017291:Clarithromycin / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D064747:Lansoprazole; D000658:Amoxicillin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D017291:Clarithromycin