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Journal of Clinical Microbiology, November 2009, p. 3493-3500, Vol. 47, No. 11
0095-1137/09/$08.00+0     doi:10.1128/JCM.00887-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role of Deletion Located between the Intermediate and Middle Regions of the Helicobacter pylori vacA Gene in Cases of Gastroduodenal Diseases{triangledown}

Hiroaki Ogiwara,1 Mitsushige Sugimoto,1 Tomoyuki Ohno,1 Ratha-Korn Vilaichone,2 Varocha Mahachai,3 David Y. Graham,1 and Yoshio Yamaoka1,4*

Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, and Baylor College of Medicine, Houston, Texas,1 Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand,2 Gastroenterology Unit, Department of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand,3 Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu-City, Oita, Japan4

Received 5 May 2009/ Returned for modification 19 June 2009/ Accepted 22 August 2009

The vacuolating cytotoxin gene of Helicobacter pylori, vacA, induces cytoplasmic vacuolation in gastric epithelial cells. Recently, the vacA intermediate (i) region, which is located between the signal (s) and middle (m) regions, was identified as a third polymorphic determinant of vacA activity. In vacA, there are approximately 81-bp deletions between the vacA i and m regions (denoted the d region). The aim was to clarify the roles of the vacA d region in relation to H. pylori-related diseases and histopathological gastric mucosal changes. We assessed the vacA signal s-, m-, i-, and d-region genotypes and cagA status in H. pylori isolates recovered from Western countries (n = 266) and East Asian countries (n = 244) by PCR. In East Asian countries, there were no relationships between the vacA genotypes and the clinical outcomes and histopathological changes. In Western countries, strains with the vacA s1, m1, i1, or d1 (no deletion) genotype significantly increased the risk for the development of gastric cancer compared with the risk from strains with the s2, m2, i2, or d2 genotype (adjusted odd ratios, 3.17 [95% confidence interval {CI}, 1.07 to 9.45] for s1, 10.65 [95% CI, 3.36 to 31.35] for m1, 8.57 [95% CI, 2.85 to 25.81] for i1, and 8.04 [95% CI, 2.67 to 24.16] for d1). The highly virulent vacA genotypes significantly enhanced neutrophil infiltration and gastric atrophy in univariant analysis, whereas only the vacA d-region genotype was significantly associated with neutrophil infiltration and gastric atrophy in both the antrum and the corpus by multiple linear regression analysis. The presence of the vacA d1 genotype in H. pylori strains could be an improved predictor of histological inflammation and the potential for atrophy compared with the presence of the vacA s-, m-, and i-region genotypes in Western countries.


* Corresponding author. Mailing address: Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center (111D), Rm. 3A-320, 2002 Holcombe Blvd., Houston, TX 77030. Phone: (713) 794-7597. Fax: (713) 795-4471. E-mail: yyamaoka{at}bcm.tmc.edu

{triangledown} Published ahead of print on 2 September 2009.


Journal of Clinical Microbiology, November 2009, p. 3493-3500, Vol. 47, No. 11
0095-1137/09/$08.00+0     doi:10.1128/JCM.00887-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.