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TLR4单核苷酸多态性与伊朗患者幽门螺杆菌相关胃部疾病的关联

Associations of a TLR4 single-nucleotide polymorphism with H. pylori associated gastric diseases in Iranian patients.

作者信息

Bagheri Nader, Azadegan-Dehkordi Fatemeh, Sanei Hosein, Taghikhani Afshin, Rahimian Ghorbanali, Salimzadeh Loghman, Hashemzadeh-Chaleshtori Morteza, Rafieian-kopaei Mahmoud, Shirzad Maryam, Shirzad Hedayatollah

机构信息

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

出版信息

Clin Res Hepatol Gastroenterol. 2014 Jun;38(3):366-71. doi: 10.1016/j.clinre.2013.12.004. Epub 2014 Feb 5.

DOI:10.1016/j.clinre.2013.12.004
PMID:24508388
Abstract

OBJECTIVE

Helicobacter pylori (H. pylori) is associated with gastric ulcer and gastric adenocarcinoma. Polymorphisms in the host genes coding for toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. But the details and association to different polymorphisms and different clinical expressions in patients infected with H. pylori (different clinical expression of H. pylori infection) remain unclear.

METHODS

A case-control study consisting of 195 patients with H. pylori infection and 241 H. pylori uninfection was conducted. Genomic DNA was extracted and genotypes of TLR4Asp299Gly polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Presence of cagA was evaluated using PCR.

RESULTS

TLR4 (Asp299Gly) G and DG alleles frequency in H. pylori infected population was significantly higher in the chronic gastritis group than in the chronic active gastritis group (P=0.021; OR, 2.409; 95% CI, 1.124-5.162). Grade mononuclear (MN) infiltration in H. pylori infected patients with DG genotype of TLR-4 Asp299Gly increased significantly. CagA positivity was more frequently associated with chronic active gastritis (P=0.017, OR=2.26, 95% CI=1.144-4.462) and grade polymorphonucler (PMN) infiltration.

CONCLUSION

TLR-4 Asp299Gly G allele substitution may be modified pattern of immune response in the gastric mucosa of H. pylori infected patients and may be H. pylori infected patients with gastritis have increased risk for the development of chronic gastritis. CagA positivity may be a risk factor for development of gastritis.

摘要

目的

幽门螺杆菌(H. pylori)与胃溃疡和胃腺癌相关。编码Toll样受体(TLR)的宿主基因多态性可能影响对该感染的先天性和适应性免疫反应,影响幽门螺杆菌易感性或疾病结局。但幽门螺杆菌感染患者中不同多态性与不同临床表型之间的具体细节及关联(幽门螺杆菌感染的不同临床表型)仍不清楚。

方法

进行了一项病例对照研究,包括195例幽门螺杆菌感染患者和241例未感染幽门螺杆菌者。提取基因组DNA,通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)评估TLR4 Asp299Gly多态性的基因型。使用PCR评估cagA的存在情况。

结果

幽门螺杆菌感染人群中TLR4(Asp299Gly)G和DG等位基因频率在慢性胃炎组显著高于慢性活动性胃炎组(P = 0.021;OR,2.409;95%CI,1.124 - 5.162)。TLR-4 Asp299Gly的DG基因型幽门螺杆菌感染患者的单核细胞(MN)浸润分级显著增加。CagA阳性更常与慢性活动性胃炎相关(P = 0.017,OR = 2.26,95%CI = 1.144 - 4.462)和多形核白细胞(PMN)浸润分级相关。

结论

TLR-4 Asp299Gly G等位基因替代可能改变幽门螺杆菌感染患者胃黏膜的免疫反应模式,可能是幽门螺杆菌感染患者发生慢性胃炎的风险增加。CagA阳性可能是胃炎发生的一个危险因素。

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