臨牀消化器内科 Vol.17 No.2(5)


特集名 PPIの長期投与
題名 PPI長期投与と遺伝子多型
発刊年月 2002年 02月
著者 古田 隆久 浜松医科大学第一内科(現 Laboratory of Molecular Pharmacology, National Cancer Institute, NIH)
著者 白井 直人 浜松医科大学第一内科
【 要旨 】 プロトンポンプ阻害剤(PPI)の血中濃度，酸分泌抑制はCYP2C19の遺伝子多型で異なる．PPIを投与すると代謝の遅い群(hetEMやPM)では代謝の速い群(homEM)に比較して酸分泌抑制作用が強く現れるため，高ガストリン血症やECL細胞の過形成をきたしやすく，また，Helicobacter pylori陽性者では胃の萎縮性変化も進行しやすいようである．さらに，hetEMやPM群ではPPIの長期投与によって血清ビタミンB12の低下をきたしやすいようである．PPIによる長期の酸分泌抑制治療の際には，CYP2C19の遺伝子多型を考慮すべきと考えられる．
Theme PPI Therapy
Title Long-Term Treatment with PPI in Relation to CYP2C19 Polymorphism
Author Takahisa Furuta First Department of Medicine, Hamamatsu University School of Medicine (Laboratoly of Molecular Pharmacology, National Cancer Institute, NIH)
Author Naohito Shirai First Department of Medicine, Hamamatsu University School of Medicine
[ Summary ] Effects of proton pump inhibitors on gastric acid secretion depend significantly on CYP2C19 genotype status. After long term treatment with a PPI, serum levels in gastrin (used as a marker of acid inhibition) and chromogranin A (used as a marker of hyper plasia of ECL cells) in those groups with heterozygous extensive metabolizers (hetEM) or poor metabolizers(PM), CYP2C19 genotypes were significantly higher in comparison to those of the homozygous extensive metabolizer(homEM) genotype group. Serum Vitamin B12 and pepsinogen I levels in the hetEM and PM groups were significantly lower than those of the homEM group inlong term therapy with a PPI. Changes in mucosal morphology and serum VitB12 during long-term treatment with a PPI are assumed to be dependent on CYP2C19 genotype status. A genotyping test for CYP2C19 could provide useful and important information for long-term treatment with a PPI.
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