Abstract
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.