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Journal of Clinical Microbiology, July 1999, p. 2306-2311, Vol. 37, No. 7
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Distinct Variants of Helicobacter pylori cagA Are Associated with vacA Subtypes

Leen-Jan van Doorn,1,* Céu Figueiredo,1,2 Ricardo Sanna,1 Martin J. Blaser,3 and Wim G. V. Quint1

Delft Diagnostic Laboratory, 2625 AD Delft, The Netherlands1; IPATIMUP and Faculty of Medicine, University of Porto, Porto, Portugal2; and Vanderbilt University, Division of Infectious Diseases, and Veterans Affairs Medical Center, Nashville, Tennessee3

Received 3 November 1998/Returned for modification 27 February 1999/Accepted 26 March 1999

The diversity of the cytotoxin-associated gene (cagA) of Helicobacter pylori was analyzed in 45 isolates obtained from nine countries. We examined variation in the 5' end of the cagA open reading frame as determined by PCR and sequencing. Phylogenetic analysis revealed the existence of at least two distinct types of cagA. One variant (cagA1) was found exclusively in strains from Europe, the United States, and Australia, whereas a novel variant (cagA2) was found in strains from East Asia. The greatest diversity between cagA1 and cagA2 was found in the first 20 amino acids of the cagA open reading frame, where several consistent insertions or deletions were observed. Additional cagA sequence variants that could be classified as separate subtypes were found in two of three Peruvian and in five of seven U.S. strains tested. The calculated isoelectric point of the first 154 amino acids of the cagA1 variants (7.52 ± 1.54) was significantly higher than that of the first 154 amino acids of the cagA2 variants (5.61 ± 0.94; P < 0.001). Most cagA2 strains contained vacA subtype s1c (P < 0.001), and in vacA m1 strains cagA1 was more frequently observed than cagA2. These results show the epidemiological relationship between cagA and vacA at the subtype level and indicate the existence of distinct H. pylori lineages that are not uniformly distributed over the globe.

* Corresponding author. Mailing address: Delft Diagnostic Laboratory, R. de Graafweg 7, 2625 AD, Delft, The Netherlands. Phone: 31-15-2604577. Fax: 31-15-2604550. E-mail: L.J.van.Doorn{at}ddl.nl.

Journal of Clinical Microbiology, July 1999, p. 2306-2311, Vol. 37, No. 7
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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