幽门螺杆菌毒力基因与临床相关性的分析

doi:10.3969/j.issn.1673-8640.2016.06.009

摘要/Abstract

摘要：

目的了解上海地区幽门螺杆菌临床分离株毒力基因携带的分子特征,探究其基因型与临床幽门螺杆菌感染性胃十二指肠疾病的相关性。方法收集514例临床胃黏膜活检样本,分离培养幽门螺杆菌;设计和合成10对幽门螺杆菌毒力基因型的特异性引物,检测临床分离的幽门螺杆菌中携带的毒力基因,并分析其与幽门螺杆菌感染相关的临床疾病[慢性浅表性胃炎、慢性萎缩性胃炎和消化性溃疡（PUD）]的相关性。结果从514例胃黏膜活检样本中分离出幽门螺杆菌129株。幽门螺杆菌分离株携带多种毒力基因,包括cagA、vacA（m1、m2、s1）、iceA1、iceA2、dupA、luxS、oipA,其中vacA s1m2基因型与iceA1⁺/iceA2⁺混合基因型增加了PUD发生的危险程度,而vacA s1m1基因型则是慢性活动性胃炎的危险因素。dupA显著增加了十二指肠溃疡的危险度。结论上海地区幽门螺杆菌携带多种毒力基因,iceA1⁺/iceA2⁺和vacA s1m2基因型可能是PUD危险因子。dupA可考虑作为十二指肠溃疡的标记分子。

关键词: 幽门螺杆菌, 毒力基因, 胃十二指肠疾病, 临床相关性

Abstract:

Objective To study the molecular characteristics of Helicobacter pylori virulence genotypes and the correlation with different Helicobacter pylori-infected gastroduodenal diseases. Methods A total of 514 gastric mucosa biopsy samples were collected.Helicobacter pylori was isolated. Ten kinds of specific probes for Helicobacter pylori virulence genotypes were designed and synthesized,and the specific virulence genes were detected. The correlation of Helicobacter pylori virulence genotypes and clinical characteristics [chronic superficial gastritis,chronic atrophic gastritis and peptic ulcer disease（PUD）] was analyzed. Results A total of 129 isolates of Helicobacter pylori were isolated from 514 gastric mucosa biopsy samples. Helicobacter pylori carried multiple kinds of virulence genotypes,such as cagA,vacA（m1,m2 and s1）,iceA1,iceA2,dupA,luxS and oipA. Genotype vacA s1m2 and the combined genotype iceA1⁺/iceA2⁺ had an increased risk for PUD. Genotype vacA s1m1 was a risk factor for chronic active gastritis,while dupA was closely associated with duodenal ulcer. Conclusions Helicobacter pylori isolated from Shanghai carrys many kinds of virulence genes,iceA1⁺/iceA2⁺ and vacA s1m2 maybe risk factors for PUD,and dupA could be considered as a duodenal ulcer-specific virulence marker.

Key words: Helicobacter pylori, Virulence genes, Gastroduodenal diseases, Clinical correlation

中图分类号:

R446.5

胡玢婕, 赵付菊, 王诗雯, 项平, 杨长青, 方毅, 陈飞, 杨峰, 赵虎, 张艳梅. 幽门螺杆菌毒力基因与临床相关性的分析[J]. 检验医学, 2016, 31(6): 479-485.

HU Binjie, ZHAO Fuju, WANG Shiwen, XIANG Ping, YANG Changqing, FANG Yi, CHEN Fei, YANG Feng, ZHAO Hu, ZHANG Yanmei. Correlation of Helicobacter pylori virulence genotypes and clinical characteristics[J]. Laboratory Medicine, 2016, 31(6): 479-485.

图/表 4

参考文献 29

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基因		引物序列（5'~3'）	片段大小（bp）
cagA	F:	AATACACCAACGCCTCCAAG	400
cagA	R:	TTGTTGCCGCTTTTGCTCTC	400
vacA s1	F:	ATGGAAATACAACAAACACAC	258
vacA s1	R:	CTGCTTGAATGCGCCAAAC	258
vacA s2	F:	ATGGAAATACAACAAACACAC	286
vacA s2	R:	CTGCTTGAATGCGCCAAAC	286
vacA m1	F:	CAATCTGTCCAATCAAGCGAG	567
vacA m1	R:	GCGTCAAAATAATTCCAAGG	567
vacA m2	F:	CAATCTGTCCAATCAAGCGAG	642
vacA m2	R:	GCGTCAAAATAATTCCAAGG	642
iceA1	F:	GTGTTTTTAACCAAAGTATC	247
iceA1	R:	CTATAGCCASTYTCTTTGCA	247
iceA2	F:	GTTGGGTATATCACAATTTAT	229/334
iceA2	R:	TTRCCCTATTTTCTAGTAGGT	229/334
dupA	F:	ATGAGTTCTATTAACAG	1 839
dupA	R:	TTAAATACTCTTCCTTATAAG	1 839
oipA	F:	CGCGGAAAGGAACGGGTTTT	519
oipA	R:	TTAGCGTCTAGCGTTCTGCC	519
luxS	F:	CTGTGCGCCCTCTAAAGTGT	261
luxS	R:	CACATGGACATGCCTAGCCT	261

基因		引物序列（5'~3'）	片段大小（bp）
cagA	F:	AATACACCAACGCCTCCAAG	400
cagA	R:	TTGTTGCCGCTTTTGCTCTC	400
vacA s1	F:	ATGGAAATACAACAAACACAC	258
vacA s1	R:	CTGCTTGAATGCGCCAAAC	258
vacA s2	F:	ATGGAAATACAACAAACACAC	286
vacA s2	R:	CTGCTTGAATGCGCCAAAC	286
vacA m1	F:	CAATCTGTCCAATCAAGCGAG	567
vacA m1	R:	GCGTCAAAATAATTCCAAGG	567
vacA m2	F:	CAATCTGTCCAATCAAGCGAG	642
vacA m2	R:	GCGTCAAAATAATTCCAAGG	642
iceA1	F:	GTGTTTTTAACCAAAGTATC	247
iceA1	R:	CTATAGCCASTYTCTTTGCA	247
iceA2	F:	GTTGGGTATATCACAATTTAT	229/334
iceA2	R:	TTRCCCTATTTTCTAGTAGGT	229/334
dupA	F:	ATGAGTTCTATTAACAG	1 839
dupA	R:	TTAAATACTCTTCCTTATAAG	1 839
oipA	F:	CGCGGAAAGGAACGGGTTTT	519
oipA	R:	TTAGCGTCTAGCGTTCTGCC	519
luxS	F:	CTGTGCGCCCTCTAAAGTGT	261
luxS	R:	CACATGGACATGCCTAGCCT	261

毒力基因	检出例数	检出率（%）
cagA
cagA⁺	85	98.8
cagA^-	1	1.2
vacA
s1⁺	86	100.0
s2⁺	0	0.0
s1s2	0	0.0
m1⁺	26	30.2
m2⁺	60	69.8
m1m2	0	0.0
s1m1	26	30.2
s1m2	60	69.8
s2m1	0	0.0
s2m2	0	0.0
iceA
iceA1⁺	64	74.4
iceA2⁺	40	46.5
iceA1⁺/ iceA2^-	43	50.0
iceA1^-/ iceA2⁺	19	22.1
iceA1⁺/ iceA2⁺	21	24.4
iceA1^-/ iceA2^-	3	3.5
dupA
dupA⁺	29	33.7
dupA^-	57	66.3
luxS
LuxS⁺	86	100.0
LuxS^-	0	0.0
oipA
oipA⁺	86	100.0
oipA^-	0	0.0

毒力基因	检出例数	检出率（%）
cagA
cagA⁺	85	98.8
cagA^-	1	1.2
vacA
s1⁺	86	100.0
s2⁺	0	0.0
s1s2	0	0.0
m1⁺	26	30.2
m2⁺	60	69.8
m1m2	0	0.0
s1m1	26	30.2
s1m2	60	69.8
s2m1	0	0.0
s2m2	0	0.0
iceA
iceA1⁺	64	74.4
iceA2⁺	40	46.5
iceA1⁺/ iceA2^-	43	50.0
iceA1^-/ iceA2⁺	19	22.1
iceA1⁺/ iceA2⁺	21	24.4
iceA1^-/ iceA2^-	3	3.5
dupA
dupA⁺	29	33.7
dupA^-	57	66.3
luxS
LuxS⁺	86	100.0
LuxS^-	0	0.0
oipA
oipA⁺	86	100.0
oipA^-	0	0.0