Polymorphisms of Helicobacter pylori HP0638 reflect geographic origin and correlate with cagA status

T. Ando, R. M. Peek, D. Pride, S. M. Levine, T. Takata, Y. C. Lee, K. Kusugami, A. Van der Ende, E. J. Kuipers, J. G. Kusters, M. J. Blaser

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Abstract

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.

Original languageEnglish
Pages (from-to)239-246
Number of pages8
JournalJournal of Clinical Microbiology
Volume40
Issue number1
DOIs
Publication statusPublished - 2002 Jan 12

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Dinucleotide Repeats
Helicobacter pylori
Protein Sorting Signals
Nuclear Family
Polymerase Chain Reaction
Far East
DNA Sequence Analysis
Membrane Potentials
Virulence
Membrane Proteins
Parents
Genotype
Mothers

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)

Cite this

Ando, T. ; Peek, R. M. ; Pride, D. ; Levine, S. M. ; Takata, T. ; Lee, Y. C. ; Kusugami, K. ; Van der Ende, A. ; Kuipers, E. J. ; Kusters, J. G. ; Blaser, M. J. / Polymorphisms of Helicobacter pylori HP0638 reflect geographic origin and correlate with cagA status. In: Journal of Clinical Microbiology. 2002 ; Vol. 40, No. 1. pp. 239-246.
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abstract = "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.",
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Ando, T, Peek, RM, Pride, D, Levine, SM, Takata, T, Lee, YC, Kusugami, K, Van der Ende, A, Kuipers, EJ, Kusters, JG & Blaser, MJ 2002, 'Polymorphisms of Helicobacter pylori HP0638 reflect geographic origin and correlate with cagA status', Journal of Clinical Microbiology, vol. 40, no. 1, pp. 239-246. https://doi.org/10.1128/JCM.40.1.239-246.2002

Polymorphisms of Helicobacter pylori HP0638 reflect geographic origin and correlate with cagA status. / Ando, T.; Peek, R. M.; Pride, D.; Levine, S. M.; Takata, T.; Lee, Y. C.; Kusugami, K.; Van der Ende, A.; Kuipers, E. J.; Kusters, J. G.; Blaser, M. J.

In: Journal of Clinical Microbiology, Vol. 40, No. 1, 12.01.2002, p. 239-246.

Research output: Contribution to journalArticle

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T1 - Polymorphisms of Helicobacter pylori HP0638 reflect geographic origin and correlate with cagA status

AU - Ando, T.

AU - Peek, R. M.

AU - Pride, D.

AU - Levine, S. M.

AU - Takata, T.

AU - Lee, Y. C.

AU - Kusugami, K.

AU - Van der Ende, A.

AU - Kuipers, E. J.

AU - Kusters, J. G.

AU - Blaser, M. J.

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N2 - 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.

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