臺灣博碩士論文加值系統

幽門螺旋桿菌分泌出來的液胞毒素(簡稱VacA)會直接使寄主細胞產生空
泡化並造成細胞傷亡。與VacA強烈相關的毒素因子CagA也被發現與寄主細
胞IL-8的分泌有關。在歐美國家的分析中發現約有六成具有cagA基因，而
vacA則被發現具有很高的鑲嵌變異性(mosaicism)。利用PCR分析173個從
台灣分離出來的幽門螺旋桿菌之cagA，發現98%帶有此基因。利用
Atherton的方法發現119個台灣菌種的vacA signal peptide皆為s1a型，
而mid-region則大部分為m2型(≧80 %)，約二成則為類似m1的m1T型(>87%
identity)，以及二株m1Tm2混合型。分析台灣菌種與vacA中間0.73-kb區
域的核酸序列，發現台灣的m2菌種與國外的m2菌種(Tx30a)頗為雷同(96 %
identity)，而m1T菌種則特別與日本某些m1型極為類似( >97 %
identity)。s1a/m1T型的戴菌者比s1a/m2型更容易有腸胃潰瘍的現象 (
p< 0.05)。總計在台灣有s1a/m1T, s1a/m2, s1a/m1Tm2這三種組合。利用
限制片段長度多樣性(RFLP)的方法，分析台灣89個幽門螺旋桿菌的基因變
異性，發現2.0-kb的vacA聚合脢連鎖反應片段以HaeIII限制脢處理的結果
共有28種不同的類型。進一步分析其urease基因，發現2.4-kb的ureA-
ureB聚合脢連鎖反應片段又可再細分出19種HaeIII限制片段長度多樣性，
且其中13種未曾見於西方文獻中。vacA每種RFLP類型都可對應特定的中間
區域之基因型( m1T, m2, m1Tm2)，表示利用限制片段長度多樣性分類法
可以彌補原本PCR分類法的不足並且vacA不同的限制片段長度多樣性可能
提供與毒性高低或臨床致病性相關的線索。

Two virulence factors encoded by the cytotoxin-associated gene
(cagA) and the vacuolating cytotoxin gene (vacA) of Helicobacter
pylori (H. pylori) are known to be associated with
gastroduodenal pathologic conditions. cagA and vacA were
characterized in 173 H. pylori isolates from Taiwanese patients
by PCR. Genotypes of vacA in 119 H. pylori isolates were
characterized by use of PCR-based typing method. The genetic
variation of mid-vacA was further analyzed by PCR-based
restriction fragment length polymorphism (RFLP). The 0.73-kb
middle region of vacA in four Taiwanese isolates and 0.43-kb C-
terminal region in two Taiwanese strains were sequenced.
Nighty-eight percent strains were characterized as cagA+. All
vacA signal peptides were s1a type. In mid-region, greater than
80% strains were identified as m2 type. About 17% strains were
m1T and two strains were typed as m1Tm2 chimeric type. DNA
sequence analysis of the 0.73-kb mid-region showed that two
Taiwanese m2 strains were highly homologous to a Western strain
Tx30a (96% identity), and that two m1T strains were nearly
identical to two m1 Japanese strains (>97% identity). The s1a/
m1T strains were shown more associated with peptic ulceration
than s1a/m2 (p< 0.05). HaeIII RFLP analysis of the 2.0-kb PCR-
amplified vacA fragment from 89 Taiwanese isolates revealed 28
distinct patterns. Each RFLP was associated with one specific
vacA middle type. Further HaeIII RFLP analysis of the 2.4-kb
ureA-ureB segment from isolates in 4 popular vacA RFLPs revealed
a high polymorphism in this locus. Thirteen new ureA-ureB RFLPs
were observed compared with 6 patterns previously published.
High prevalence of cagA+ and s1a strains suggested cagA
phenotype and vacA signal sequence could not be used as markers
of high-risk patients in Taiwan. The vacA polymorphisim might
be associated with increased virulence and thus with severity of
clinical symptoms.