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Journal of Clinical Microbiology, January 2002, p. 239-246, Vol. 40, No. 1
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.1.239-246.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Polymorphisms of Helicobacter pylori HP0638 Reflect Geographic Origin and Correlate with cagA Status

T. Ando,1,2,3* R. M. Peek,2 D. Pride,1,4 S. M. Levine,1 T. Takata,1 Y.-C. Lee,1 K. Kusugami,3 A. van der Ende,5 E. J. Kuipers,6 J. G. Kusters,6 and M. J. Blaser1,2,7

Department of Medicine, New York University School of Medicine,1 Department of Medicine,2 First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan,3 Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee,4 Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam,5 Department of Gastroenterology and Hepatology, University Hospital Dijkzigt, Rotterdam, The Netherlands,6 Department of Veterans Affairs Medical Center, New York, New York7

Received 12 June 2001/ Returned for modification 27 August 2001/ Accepted 15 October 2001

Since the associations between Helicobacter pylori genotype and disease differ in Asia and the West, we investigated the correlation between HP0638, encoding an outer membrane protein, and potential markers of virulence (cagA, vacA, and iceA). For 109 strains from nine countries, the status of cagA, vacA, and iceA was determined by PCR and/or a line probe assay. We also studied 18 strains from 8 patients (parents and 6 daughters) from a Dutch family and paired strains collected on average 8 years apart from 11 patients. When the HP0638 signal sequences were amplified by PCR and DNA sequence determinations were performed, 89 (96%) of 93 cagA-positive strains had HP0638 in frame, versus none (0%) of 16 cagA-negative strains (P < 0.001). Among strains in which HP0638 was in frame, a six-CT dinucleotide repeat pattern was dominant in Western countries (23 of 33 strains [70%]), while a pattern of three CT repeats with another CT after four T’s (3 + 1-CT-repeat pattern) was dominant in East Asia (31 of 46 strains [67%]); however, specific CT repeat patterns did not correlate with clinical outcome. HP0638 phylogenetic trees also showed geographic characters. The HP0638 frame status and CT dinucleotide repeat patterns were identical for 9 of 11 pairs of strains obtained on average 8 years apart from individuals and the 15 strains obtained from the mother and all six daughters. Thus, HP0638 frame status and cagA status are strongly correlated. The CT dinucleotide repeat pattern in the putative HP0638 signal sequence has geographic characters and appears stable in particular patients and families over a period of years. Analysis of HP0638 CT polymorphisms may serve as a new typing system to discriminate H. pylori isolates for epidemiological purposes.

* Corresponding author. Mailing address: First Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. Phone: 81-52-744-2144. Fax: 81-52-744-2157. E-mail: andot01{at}mcmbox.med.nyu.edu.

Journal of Clinical Microbiology, January 2002, p. 239-246, Vol. 40, No. 1
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.1.239-246.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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