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Journal of Clinical Microbiology, June 2001, p. 2369-2370, Vol. 39, No. 6
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.6.2369-2370.2001
LETTERS TO THE EDITOR
Clarifications Regarding the 3' Repeat Region of the
cagA Gene in Helicobacter pylori and
Clinical Outcome
 |
LETTER |
In a recent issue, Rota et al. (2) reported a study
regarding the 3' repeat region of the cagA gene of
Helicobacter pylori in which they classified the
cagA 3' region into three types (A, B/D, and C) according to
our previous report (5). They reported no association
between 3' repeat region subtypes and clinical outcome. However,
multiple subtypes of the cagA repeat region were associated
with gastric ulcer. Unfortunately, the PCR primers they used are
located outside of the repeat regions, and strains isolated from East
Asian and non-Asian countries are detected by PCR using these primers.
As we previously described, the sequences of the second repeat regions
in strains from East Asia are completely different from those in
strains from non-Asian countries (3, 4). Non-Asian strains
possess 102-bp second repeat regions, and East Asian strains possess
162-bp second repeat regions (3-5). Therefore, subtypes A
through D cannot be applied to non-Asian strains. In East Asian
strains, types A (around 648 bp) and B (around 756 bp) have one second
repeat region and types C (around 810 bp) and D (around 756 bp) have
two second repeat regions. The expected lengths of the PCR products in
East Asian strains are equal to (423 ~ 432) + (57 × f) + (162 × s), where f is the number of first repeat regions and s is the number of second
repeat regions. In contrast, the expected lengths of PCR products in non-Asian strains are equal to (486 ~ 498) + (57 × f) + (102 × s) bp. We found that typically (>95%)
there was only one first repeat region in non-Asian strains (3,
4) such that the expected lengths of the PCR products are
(543 ~ 555) + (102 × s) bp. Thus, 650-, 750-, and 850-bp fragments indicate H. pylori with one, two,
and three cagA non-Asian type second repeat regions, respectively, which is in complete agreement with data by Rota et al.
confirming that the Brazilian strains have a non-Asian cagA
structure. We reported that non-Asian H. pylori strains with three or more second repeat regions were associated with gastric atrophy and intestinal metaplasia (3). Recently, Kidd et
al. reported that, compared to the prevalence in patients with
gastritis alone, the prevalence of the shortest PCR fragment in the 3'
region of the cagA gene was high in peptic ulcer patients
and the prevalence of the longest fragment was high in patients with
gastric cancer (1). Rota et al. also noted that the
presence of multiple genotypes in the cagA repeat region was
associated with gastric ulcer (which is typically associated with
pangastritis and some atrophy) but not with duodenal ulcer (which
typically has a nonatrophic gastritis) (2). Although
neither Rota et al. nor Kidd et al. provided data about the presence of
atrophy, both reports are consistent with the hypothesis that
cagA second repeat regions are associated with the
premalignant condition of gastric atrophy. Finally, the "Japanese
methodology" was developed in Houston, Tex. (3).
| |
FOOTNOTES |
*
Phone: (713) 794-7234
Fax: (713) 790-1040
E-mail: yyamaoka{at}bcm.tmc.edu
| |
REFERENCES |
| 1.
|
Kidd, M.,
A. J. Lastovica,
J. C. Atherton, and J. A. Louw.
1999.
Heterogeneity in the Helicobacter pylori vacA and cagA genes: association with gastroduodenal disease in South Africa?
Gut
45:499-502[Abstract/Free Full Text].
|
| 2.
|
Rota, C. A.,
J. C. Pereira-Lima,
C. Blaya, and N. B. Nardi.
2001.
Consensus and variable region PCR analysis of Helicobacter pylori 3' region of cagA gene in isolates from individuals with or without peptic ulcer.
J. Clin. Microbiol.
39:606-612[Abstract/Free Full Text].
|
| 3.
|
Yamaoka, Y.,
H. M. T. El-Zimaity,
O. Gutierrez,
N. Figura,
J. G. Kim,
T. Kodama,
K. Kashima, and D. Y. Graham.
1999.
Relationship between subtypes of the cagA 3' repeat region, gastric histology, and susceptibility to low pH.
Gastroenterology
117:342-349[CrossRef][Medline].
|
| 4.
|
Yamaoka, Y.,
M. S. Osato,
A. R. Sepulveda,
O. Gutierrez,
N. Figura,
J. G. Kim,
T. Kodama,
K. Kashima, and D. Y. Graham.
2000.
Molecular epidemiology of Helicobacter pylori: separation of H. pylori from East Asian and non-Asian countries.
Epdemiol. Infect.
124:91-96[CrossRef][Medline].
|
| 5.
|
Yamaoka, Y.,
T. Kodama,
K. Kashima,
D. Y. Graham, and A. R. Sepulveda.
1998.
Variants of the 3' region of the cagA gene in Helicobacter pylori isolates from different H. pylori-associated diseases.
J. Clin. Microbiol.
36:2258-2263[Abstract/Free Full Text].
|
| | | | |
Yoshio Yamaoka*
David Y. Graham
Department of Medicine
Veterans Affairs Medical Center (111D)
and Baylor
College of Medicine
2002 Holcombe Blvd.
Houston, Texas 77030
|
| |
AUTHORS' REPLY |
We are grateful to Dr. Yamaoka and Dr. Graham for their clarifying
comments. The first point we want to make is that our primary goal was
to verify if different cagA-positive H. pylori
subtypes were related to distinct clinical outcomes in our population. At the time we designed our study, the only paper describing a classification method for different H. pylori subtypes was
the one published by Yamaoka et al. in this journal (3).
Based on this reference, we used primers flanking the repeat regions in
our population of patients (the population studied was predominantly European derived) (1). We believed that these primers were appropriate to use in our study because we knew from the published cagA-positive sequences (GenBank accession numbers AFO01357
and L117714) that they were not specific for Asian strains.
Furthermore, this was later confirmed in another report from Yamaoka et
al. (2) which showed that the flanking repeat region
primers (named entire repeat region primers by them) can be used to
detect H. pylori strains from Asian and non-Asian
populations. We used the term "Japanese" to describe this
methodology only because the original study was done to classify the
cagA subtypes in a population of Japanese patients who
underwent gastric endoscopy at the Hospital of the Kyoto Prefectural
University of Medicine, Kyoto, Japan (3). However, with
the information provided by Yamaoka and Graham that this technique
comes from the United States, we agree that this is probably not the
best term to describe the method. Second, it is important to remember
that we did not intend to develop a diagnostic method capable of
distinguishing between Asian and non-Asian H. pylori
strains. Finally, we agree with the hypothesis raised by Yamaoka and
Graham that the cagA second repeat region may be an
important predictor of prognosis and that the presence of subtypes with
a longer fragment length may be associated with premalignant
conditions. It would be very important to continue this investigation
using a larger sample of patients, preferably of different ethnic
backgrounds, in order to prove this hypothesis.
| |
FOOTNOTES |
*
Phone or fax: 55-51-2351451
E-mail: nlabmol{at}zaz.com.br
| |
REFERENCES |
| 1.
|
Rota, C. A.,
J. C. Pereira-Lima,
C. Blaya, and N. B. Nardi.
2001.
Consensus and variable region PCR analysis of Helicobacter pylori 3' region of cagA gene in isolates from individuals with or without peptic ulcer.
J. Clin. Microbiol.
39:602-612.
|
| 2.
|
Yamaoka, Y.,
M. S. Osato,
A. R. Sepulveda,
O. Gutierrez,
N. Figura,
J. G. Kim,
T. Kodama,
K. Kashima, and D. Y. Graham.
2000.
Molecular epidemiology of Helicobacter pylori: separation of H. pylori from East Asian and non-Asian countries.
Epidemiol. Infect.
124:91-96.
|
| 3.
|
Yamaoka, Y.,
T. Kodama,
K. Kashima,
D. Y. Graham, and A. R. Sepulveda.
1998.
Variants of the 3' region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases.
J. Clin. Microbiol.
36:2258-2263.
|
| | | | |
Cláudia Augustin Rota*
Júlio C. Pereira-Lima
Nance B. Nardi
Laboratory of Molecular and Cellular Biology
NETLAB-Laboratório Bioclínico
Av. Praia de Belas 2166, CEP 90.110-000,
Porto Alegre, RS, Brazil
|
Journal of Clinical Microbiology, June 2001, p. 2369-2370, Vol. 39, No. 6
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.6.2369-2370.2001
