Association of Helicobacter pylori infection with Toll-like receptor-4 Thr399Ile polymorphism increased the risk of peptic ulcer development in North of Iran
Mehdi Tourani
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
Search for more papers by this authorMaryam Habibzadeh
Student Research Committee, Babol University of Medical Sciences, Babol, Iran
Search for more papers by this authorJavad Shokri-Shirvani
Department of Internal Medicine, Babol University of Medical Sciences, Babol, Iran
Search for more papers by this authorOmid Teymournejad
Faculty of Medical Sciences, Department of Bacteriology, Tarbiat Modares University, Tehran, Iran
Search for more papers by this authorAmrollah Mostafazadeh
Department of Immunology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
Search for more papers by this authorSoraya Khafri
Biostatistics & Epidemiology Department, Babol University of Medical Sciences, Babol, Iran
Search for more papers by this authorCorresponding Author
Hamid Reza Nouri
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
Hamid Reza Nouri, Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Ganjafrooz Street, 47176-47745, Babol, Iran. e-mail: [email protected]Search for more papers by this authorMehdi Tourani
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
Search for more papers by this authorMaryam Habibzadeh
Student Research Committee, Babol University of Medical Sciences, Babol, Iran
Search for more papers by this authorJavad Shokri-Shirvani
Department of Internal Medicine, Babol University of Medical Sciences, Babol, Iran
Search for more papers by this authorOmid Teymournejad
Faculty of Medical Sciences, Department of Bacteriology, Tarbiat Modares University, Tehran, Iran
Search for more papers by this authorAmrollah Mostafazadeh
Department of Immunology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
Search for more papers by this authorSoraya Khafri
Biostatistics & Epidemiology Department, Babol University of Medical Sciences, Babol, Iran
Search for more papers by this authorCorresponding Author
Hamid Reza Nouri
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
Hamid Reza Nouri, Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Ganjafrooz Street, 47176-47745, Babol, Iran. e-mail: [email protected]Search for more papers by this authorAbstract
Toll-like receptor-4 (TLR4) polymorphisms may influence host immune response against Helicobacter pylori (H. pylori). This study aimed to investigate whether TLR4 polymorphisms are associated with H. pylori susceptibility and risk of peptic ulcer development or not. The TLR4 + 3725 G/C polymorphism was studied using polymerase chain reaction with confronting two-pair primers (PCR–CTPP). In addition, TLR4 Asp299Gly and Thr399Ile polymorphisms were evaluated by PCR-restriction fragment length polymorphism (RFLP). There was no significant difference in TLR4 + 3725 G/C and Asp299Gly genotype frequencies between non-peptic ulcer (NPUD) and peptic ulcer (PUD) individuals in the context of peptic ulcer development and susceptibility to infection with H. pylori. Nevertheless, a significant association with increased risk for PUD development was observed for polymorphism TLR4 Thr399Ile [odds ratio (OR) = 4.2; 95% confidence interval (CI) = 1.35–13.26; p = 0.01]. Correspondingly, TLR4 Thr399Ile polymorphism was associated with H. pylori susceptibility (OR = 0.27; 95% CI = 0.08–0.88; p = 0.04). In addition, TLR4 Thr399Ile polymorphism increased 4.2-fold, the risk of peptic ulcer development in individuals infected by H. pylori carrying CT + TT genotype. Our results showed that TLR4 Thr399Ile polymorphism along with H. pylori infection may play critical roles in peptic ulcer development in North of Iran.
References
- 1Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 2006; 19: 449–90.
- 2Pandey R, Misra V, Misra S, Dwivedi M, Kumar A, Tiwari BK. Helicobacter pylori and gastric cancer. Asian Pac J Cancer Prev 2010; 11: 583–8.
- 3Mockenhaupt FP, Cramer JP, Hamann L, Stegemann MS, Eckert J, Oh N-R, et al. Toll-like receptor (TLR) polymorphisms in African children: common TLR-4 variants predispose to severe malaria. Proc Natl Acad Sci USA 2006; 103: 177–82.
- 4Hishida A, Matsuo K, Goto Y, Mitsuda Y, Hiraki A, Naito M, et al. Toll-like receptor 4 + 3725 G/C polymorphism, Helicobacter pylori seropositivity, and the risk of gastric atrophy and gastric cancer in Japanese. Helicobacter 2009; 14: 47–53.
- 5Gasque P. Complement: a unique innate immune sensor for danger signals. Mol Immunol 2004; 41: 1089–98.
- 6Takeda K, Akira S. Toll-like receptors in innate immunity. Int Immunol 2005; 17: 1–14.
- 7Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010; 11: 373–84.
- 8Zhou L, Zheng D, Wang S, Zhu J, Jia Y, Sun D, et al. Genetic association of Toll-like receptor 4 gene and coronary artery disease in a Chinese Han population. SpringerPlus 2016; 5: 1533.
- 9Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 2011; 34: 637–50.
- 10Schmausser B, Andrulis M, Endrich S, Lee S, Josenhans C, Muller Hermelink HK, et al. Expression and subcellular distribution of toll-like receptors TLR4, TLR5 and TLR9 on the gastric epithelium in Helicobacter pylori infection. Clin Exp Immunol 2004; 136: 521–6.
- 11Smith SM. Role of Toll-like receptors in Helicobacter pylori infection and immunity. World J Gastrointest Pathophysiol 2014; 5: 133–46.
- 12Salama NR, Hartung ML, Muller A. Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat Rev Microbiol 2013; 11: 385–99.
- 13Garza-González E, Bosques-Padilla FJ, El-Omar E, Hold G, Tijerina-Menchaca R, Maldonado-Garza HJ, et al. Role of the polymorphic IL-1B, IL-1RN and TNF-A genes in distal gastric cancer in Mexico. Int J Cancer 2005; 114: 237–41.
- 14Kiechl S, Wiedermann CJ, Willeit J. Toll-like receptor 4 and atherogenesis. Ann Med 2003; 35: 164–71.
- 15Hold GL, Rabkin CS, Chow WH, Smith MG, Gammon MD, Risch HA, et al. A functional polymorphism of toll-like receptor 4 gene increases risk of gastric carcinoma and its precursors. Gastroenterology 2007; 132: 905–12.
- 16Lorenz E, Frees KL, Schwartz DA. Determination of the TLR4 genotype using allele-specific PCR. Biotechniques 2001; 31: 22–4.
- 17Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 2000; 25: 187–91.
- 18Liu R, Mo YY, Wang HL, Tan Y, Wen XJ, Deng MJ, et al. The relationship between toll like receptor 4 gene rs4986790 and rs4986791 polymorphisms and sepsis susceptibility: a meta-analysis. Sci Rep 2016; 6: 38947.
- 19Senhaji N, Diakite B, Serbati N, Zaid Y, Badre W, Nadifi S. Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms: new data and a meta-analysis. BMC Gastroenterol 2014; 14: 206.
- 20Achyut B, Ghoshal UC, Moorchung N, Mittal B. Association of Toll-like receptor–4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions. Hum Immunol 2007; 68: 901–7.
- 21Nasiri H, Forouzandeh M, Rasaee M, Rahbarizadeh F. Modified salting-out method: high-yield, high-quality genomic DNA extraction from whole blood using laundry detergent. J Clin Lab Anal 2005; 19: 229–32.
- 22Michel O, LeVan TD, Stern D, Dentener M, Thorn J, Gnat D, et al. Systemic responsiveness to lipopolysaccharide and polymorphisms in the toll-like receptor 4 gene in human beings. J Allergy Clin Immunol 2003; 112: 923–9.
- 23Hamajima N, Saito T, Matsuo K, Matsuo K, Kozaki KI, Takahashi T, Tajima K. Polymerase chain reaction with confronting two-pair primers for polymorphism genotyping. Cancer Sci 2000; 91: 865–8.
- 24Teshima S, Rokutan K, Nikawa T, Kishi K. Guinea pig gastric mucosal cells produce abundant superoxide anion through an NADPH oxidase-like system. Gastroenterology 1998; 115: 1186–96.
- 25Tahara T, Arisawa T, Shibata T, Hirata I, Nakano H. Absence of common polymorphisms of toll like receptor 4 (TLR4): Asp299Gly, Thr399Ile in patients with gastroduodenal diseases in Japan. J Clin Biochem Nutr 2007; 40: 62–5.
- 26Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 2009; 22: 240–73.
- 27Michalkiewicz J, Helmin-Basa A, Grzywa R, Czerwionka-Szaflarska M, Szaflarska-Poplawska A, Mierzwa G, et al. Innate immunity components and cytokines in gastric mucosa in children with Helicobacter pylori infection. Mediators Inflamm 2015; 2015: 1–7.
10.1155/2015/176726 Google Scholar
- 28Ohto U, Yamakawa N, Akashi-Takamura S, Miyake K, Shimizu T. Structural analyses of human Toll-like receptor 4 polymorphisms D299G and T399I. J Biol Chem 2012; 287: 40611–7.
- 29Santini D, Angeletti S, Ruzzo A, Dicuonzo G, Galluzzo S, Vincenzi B, et al. Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in gastric cancer of intestinal and diffuse histotypes. Clin Exp Immunol 2008; 154: 360–4.
- 30Hofner P, Gyulai Z, Kiss ZF, Tiszai A, Tiszlavicz L, Toth G, et al. Genetic polymorphisms of NOD1 and IL-8, but not polymorphisms of TLR4 genes, are associated with Helicobacter pylori-induced duodenal ulcer and gastritis. Helicobacter 2007; 12: 124–31.
- 31Hold GL, Berry S, Saunders KA, Drew J, Mayer C, Brookes H, et al. The TLR4 D299G and T399I SNPs are constitutively active to up-regulate expression of Trif-dependent genes. PLoS ONE 2014; 9: e111460.
- 32Kim YS, Hwang YJ, Kim SY, Yang SM, Lee KY, Park IB. Rarity of TLR4 Asp299Gly and Thr399Ile polymorphisms in the Korean population. Yonsei Med J 2008; 49: 58–62.
- 33Oostenbrug LE, Drenth JP, de Jong DJ, Nolte IM, Oosterom E, van Dullemen HM, et al. Association between Toll-like receptor 4 and inflammatory bowel disease. Inflamm Bowel Dis 2005; 11: 567–75.
- 34Rigoli L, Romano C, Caruso RA, Lo Presti MA, Di Bella C, Procopio V, et al. Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease. World J Gastroenterol 2008; 14: 4454–6.
