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蛋白酪氨酸磷酸酶非受体型11(PTPN11)基因多态性与胃萎缩的关联——在乌兹别克斯坦与日本相反。

Associations between a PTPN11 polymorphism and gastric atrophy--opposite in Uzbekistan to that in Japan.

作者信息

Hamajima Nobuyuki, Rahimov Bakhodir, Malikov Yusuf, Abdiev Shavkat, Ahn Keun Soo, Bahramov Saidkarim, Kawai Sayo, Nishio Kazuko, Naito Mariko, Goto Yasuyuki

机构信息

Department of Preventive Medicine/Medical Decision Making, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550 Japan.

出版信息

Asian Pac J Cancer Prev. 2008 Apr-Jun;9(2):217-20.

PMID:18712962
Abstract

Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) of gastric epithelial cells interacts with cagA from Helicobacter pylori (H. pylori). Our previous studies found the AA genotype of a G/A single nucleotide polymorphism at intron 3 (rs2301756) of PTPN11 gene, which encodes SHP-2, to be associated with a lower risk of gastric atrophy. The present study aimed to examine the association with gastric atrophy among the subjects of a case-control study of peptic ulcer disease (PUD) conducted in the Uzbek Republic. Cases were 95 patients (61 males and 34 females) with PUD aged 16 to 85 years. Controls were 102 hospital volunteers (42 males and 60 females) including 42 patients with miscellaneous diseases, aged 15 to 75 years. Gastric atrophy was evaluated with serum pepsinogens (PG1<70 ng/ml and PG1/PG2<3). Polymorphisms of PTPN11 at intron 3 (rs2301756) and intron10 (rs12229892) were genotyped with PCR with confronting two-pair primers (PCR-CTPP). Anti-cagA IgG antibody was detected in 93.7% of cases and 77.5% in controls. Gastric atrophy was observed in 24.2% of the PUD patients and 33.3% in the controls. The A allele at intron 3 was completely linked to the G allele at intron 10. The age, sex, and group (cases and controls) adjusted odds ratio of gastric atrophy was 0.18 (95% confidence interval, 0.04-0.86) for intron 3 GG genotype relative to AA genotype. Since the finding was opposite to that among Japanese, the H. pylori strains and/or lifestyle in Uzbekistan might modify the association.

摘要

胃上皮细胞中含Src同源2结构域的蛋白酪氨酸磷酸酶2(SHP-2)与幽门螺杆菌(H. pylori)的cagA相互作用。我们之前的研究发现,编码SHP-2的PTPN11基因内含子3(rs2301756)处G/A单核苷酸多态性的AA基因型与较低的胃萎缩风险相关。本研究旨在调查在乌兹别克共和国进行的消化性溃疡病(PUD)病例对照研究中,研究对象与胃萎缩之间的关联。病例为95例年龄在16至85岁之间的PUD患者(61例男性和34例女性)。对照为102名医院志愿者(42例男性和60例女性),包括42例患有其他疾病的患者,年龄在15至75岁之间。通过血清胃蛋白酶原(PG1<70 ng/ml且PG1/PG2<3)评估胃萎缩情况。采用两对引物对PCR(PCR-CTPP)对PTPN11基因内含子3(rs2301756)和内含子10(rs12229892)的多态性进行基因分型。93.7%的病例和77.5%的对照检测到抗cagA IgG抗体。24.2%的PUD患者和33.3%的对照观察到胃萎缩。内含子3的A等位基因与内含子10的G等位基因完全连锁。相对于AA基因型,内含子3 GG基因型的年龄、性别和组(病例和对照)调整后的胃萎缩优势比为0.18(95%置信区间,0.04 - 0.86)。由于这一发现与日本人中的情况相反,乌兹别克斯坦的幽门螺杆菌菌株和/或生活方式可能会改变这种关联。

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J Gastrointest Cancer. 2014 Sep;45(3):319-24. doi: 10.1007/s12029-014-9608-9.
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Association between TNF-α and IL-1β genotypes vs Helicobacter pylori infection in Indonesia.
TNF-α 和 IL-1β 基因型与印度尼西亚幽门螺杆菌感染的关联。
World J Gastroenterol. 2013 Dec 14;19(46):8758-63. doi: 10.3748/wjg.v19.i46.8758.
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Association of polymorphism of PTPN 11 encoding SHP-2 with gastric atrophy but not gastric cancer in Helicobacter pylori seropositive Chinese population.在中国幽门螺杆菌血清阳性人群中,编码 SHP-2 的 PTPN11 多态性与胃萎缩相关,但与胃癌无关。
BMC Gastroenterol. 2012 Jul 12;12:89. doi: 10.1186/1471-230X-12-89.
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Interleukin-8 T-251A polymorphism was associated with positive anti-p53 antibodies in Uzbekistan population.白细胞介素-8 T-251A多态性与乌兹别克斯坦人群中抗p53抗体阳性相关。
Nagoya J Med Sci. 2009 Sep;71(3-4):151-6.
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