Sequence analysis and clinical significance of the iceA gene from Helicobacter pylori strains in Japan

Sequence analysis and clinical significance of the iceA gene from Helicobacter pylori strains in Japan
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DOI:
10.1128/jcm.38.2.483-488.2000
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发表时间:
2000-02-01
影响因子:
9.4
通讯作者:
Kuriyama, M
Kuriyama, M
中科院分区:
医学2区
文献类型:
--
作者:
Ito, Y;Azuma, T;Kuriyama, M

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幽门螺杆菌iceA基因最近被确定为西方人群消化性溃疡发展的遗传标记。为了评估iceA亚型幽门螺杆菌与消化性溃疡的关系,对140株日本临床分离株(88株来自福井,52株来自冲绳)进行了特征分析。我们还对25个代表性日本菌株的iceA1基因进行了序列分析,以确定溃疡组和胃炎组之间iceA1基因的差异。iceA1基因型与两个区域消化性溃疡的存在无关。此外,序列分析导致在iceA1开放阅读框中鉴定出5个缺失和5个点突变(无义突变或1-bp插入),与先前发表的序列相对应。在每个地区的两个临床组(溃疡和胃炎组)中都发现了这些突变。局部DNA序列分析显示,所有5个缺失的终点都与直接重复序列一致。与菌株60190相比,我们还发现4株菌株携带更长的iceA1开放阅读框。总之,携带iceA1菌株似乎不是日本受试者消化性溃疡的危险因素。在一些消化性溃疡患者分离株中iceA1基因的关键突变表明,在日本,IceA不参与消化性溃疡的发病机制。我们还发现了与iceA1中直接重复相关的缺失热点,并且在复制过程中倾向于滑移错配对事件的小缺失模型。我们发现iceA1序列变异可能是幽门螺杆菌群体遗传学分析的有用工具。
The Helicobacter pylori iceA gene was recently identified as a genetic marker for the development of peptic ulcer in a Western population. To assess the significance of iceA subtypes of H. pylori in relation to peptic ulcer, 140 Japanese clinical isolates (88 from Fukui and 52 from Okinawa) were characterized. Sequence analysis of the iceA1 gene from 25 representative Japanese strains was also carried out to identify the differences in iceA between the ulcer group and the gastritis group. The iceA1 genotype was not correlated with the presence of peptic ulceration in either area. In addition, sequence analysis led to identification of five deletions and five point mutations (a nonsense mutation or a 1-bp insertion) within the iceA1 open reading frame corresponding to previously published sequences. These mutations were identified in both clinical groups (ulcer and gastritis groups) in each area. Local DNA sequence analysis revealed that the endpoints of all five deletions coincided with direct repeats. We also found four strains that carried longer iceA1 open reading frames compared with that for strain 60190. In conclusion, carriage of an iceA1 strain does not seem to be a risk factor for peptic ulcer in Japanese subjects. The critical mutations in the iceA1 gene in some isolates from patients with peptic ulcers suggested that IceA does not participate in the pathogenesis of peptic ulcer in Japan. We also found deletion hot spots that were associated,vith direct repeats in iceA1 and that favored a small-deletion model of slipped mispairing events during replication. We showed that iceA1 sequence variations may be useful tools for analysis of the population genetics of H. pylori.