Furuta Takahisa, Sagehashi Yukiko, Shirai Naohito, Sugimoto Mitsushige, Nakamura Akiko, Kodaira Makoto, Kenmotsu Kazumi, Nagano Makoto, Egashira Tohru, Ueda Koji, Yoneyama Masao, Ohashi Kyoichi, Ishizaki Takashi, Hishida Akira
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Clin Gastroenterol Hepatol. 2005 Jun;3(6):564-73. doi: 10.1016/s1542-3565(04)00779-7.
BACKGROUND & AIMS: The relationship between single nucleotide polymorphisms (SNPs) and clinical outcomes has been intensively studied. We intended to determine SNPs of CYP2C19 and 23S rRNA of Helicobacter pylori by using rapid urease test (RUT)-positive gastric mucosal samples.
One hundred thirty-nine patients with H pylori -positive results based on RUT completed 1-week treatment with lansoprazole 30 mg twice a day, clarithromycin 200 mg 3 times daily, and amoxicillin 500 mg 3 times daily. SNPs from adenine to guanine at positions 2142 and 2143 of 23S rRNA of H pylori (A2142G and A2143G) and SNPs from guanine to adenine at positions 681 in exon 5 (* 2 ) and 636 in exon 4 (* 3 ) of CYP2C19 were determined by the serial invasive signal amplification reaction assay by using DNAs extracted from gastric tissue samples already used for RUT. Minimum inhibitory concentrations of clarithromycin for H pylori were determined by culture test. CYP2C19 genotypes were classified into the rapid metabolizer (* 1 /* 1 ), intermediate metabolizer (* 1 /* 2 or * 1 /* 3 ), and poor metabolizer (* 2 /* 2 , * 2 /* 3 , or * 3 /* 3 ) groups.
H pylori strains with A2142G or A2143G mutation had higher minimum inhibitory concentrations for clarithromycin. Cure rates in rapid, intermediate, and poor metabolizer groups were 57.8% (95% confidence interval, 42.1%-72.4%), 88.2% (78.1%-94.8%), and 92.3% (74.9%-99.1%), respectively ( P < .001). Cure rates in strains with and without A2142G or A2143G mutation were 48.3% (29.4%-67.5%) and 87.3% (79.5%-92.7%), respectively ( P < .001).
SNPs of CYP2C19 and 23S rRNA of H pylori using RUT-positive gastric mucosal samples could be predictable determinants for H pylori eradication by triple therapy.
单核苷酸多态性(SNP)与临床结局之间的关系已得到深入研究。我们旨在通过使用快速尿素酶试验(RUT)阳性的胃黏膜样本,确定幽门螺杆菌CYP2C19和23S rRNA的SNP。
139例基于RUT检测结果为幽门螺杆菌阳性的患者,接受了为期1周的治疗,即每天两次服用30mg兰索拉唑、每日3次服用200mg克拉霉素以及每日3次服用500mg阿莫西林。通过使用从已用于RUT的胃组织样本中提取的DNA,采用序列侵入信号扩增反应分析法,确定幽门螺杆菌23S rRNA第2142和2143位从腺嘌呤到鸟嘌呤的SNP(A2142G和A2143G)以及CYP2C19第5外显子681位(*2)和第4外显子636位(*3)从鸟嘌呤到腺嘌呤的SNP。通过培养试验确定幽门螺杆菌对克拉霉素的最低抑菌浓度。CYP2C19基因型分为快代谢型(*1/*1)、中代谢型(*1/2或1/*3)和慢代谢型(*2/*2、*2/3或3/*3)组。
具有A2142G或A2143G突变的幽门螺杆菌菌株对克拉霉素的最低抑菌浓度较高。快代谢型、中代谢型和慢代谢型组的治愈率分别为57.8%(95%置信区间,42.1%-72.4%)、88.2%(78.1%-94.8%)和92.3%(74.9%-99.1%)(P<.001)。有和没有A2142G或A2143G突变菌株的治愈率分别为48.3%(29.4%-67.5%)和87.3%(79.5%-92.7%)(P<.001)。
使用RUT阳性胃黏膜样本检测幽门螺杆菌CYP2C19和23S rRNA的SNP,可能是三联疗法根除幽门螺杆菌的可预测决定因素。