ارتباط پلی مورفیسم ژن اینترلوکین-27(-964 A/G) با تظاهرات بالینی عفونت هلیکوباکتر پیلوری
محورهای موضوعی : ایمنی شناسی
الهام معظمیان
1
(استادیار، دانشگاه آزاد اسلامی، واحد علوم و تحقیقات، گروه میکروب شناسی، فارس)
منوچهر رسولی
2
(استادیار، مرکز تحقیقات میکروب شناسی بالینی استاد البرزی، دانشگاه علوم پزشکی شیراز)
صدف عصایی
3
(کارشناس، مرکز تحقیقات میکروب شناسی بالینی استادالبرزی، دانشگاه علوم پزشکی شیراز)
کلید واژه: هلیکوباکتر پیلوری, گاستریت, پلی مورفیسم, اینترلوکین-27, سرطان معده,
چکیده مقاله :
سابقه و هدف: هلیکوباکتر پیلوری یکی از شایع ترین عوامل بیماری زای باکتریایی در انسان می باشد. تقریباً نیمی از جمعیت دنیا با این باکتری آلوده اند و به عنوان عامل مهم بیماری های گوارشی مانند التهاب مزمن معده، بیماری زخم معده و سرطان معده شناخته شده است. اینترلوکین-27 یک سایتوکاین پیش التهابی می‌باشد که توسط سلول‌های (CD4+) Th ترشح شده و از طریق القای فاکتورهای مختلف باعث ایجاد و تقویت التهاب می‌شود. این مطالعه با هدف بررسی ارتباط پلی‌مورفیسم ژن اینترلوکین-27 در بیماران مبتلا به هلیکوباکتر پیلوری و مقایسه آن با گروه شاهد انجام شد. مواد و روش ها: این مطالعه مورد-شاهدی بر روی 434 نفر انجام گردید. این افراد شامل 149 بیمار (100 مورد گاستریت و 49 مورد زخم معده)، 58 نفر افراد دارای گاستریت بدون هلیکوباکتر پیلوری و 227 فرد سالم بودند. DNA ژنومی با روش نمکی استخراج گردید. ژنوتیپ‌های حاصل از پلی‌مرفیسم اینترلوکین-27(-964 A/G) با روش PCR-RFLP مورد بررسی قرار گرفت. نتایج بین گروه های بیماران و شاهد مقایسه گردید. یافته ها: فراوانی آلل A در بیماران مبتلا به زخم معده بیشتر (78.5 درصد) از فراوانی آن در گروه سالم (75.6 درصد) بود. اما این تفاوت از نظر آماری معنی‌دار نبود. همچنین فراوانی ژنوتیپ ها نیز بین گروه های مختلف فاقد تفاوت معنی دار آماری بود. نتیجه گیری: نتایج حاصل از این تحقیق نشان داد که پلی مورفیسم ژن اینترلوکین-27(-964 A/G) دلیل تفاوت تظاهرات بالینی حاصل از عفونت با هلیکوباکتر نمی باشد. بنابراین مطالعه سایر مناطق پلی مورفیک اینترلوکین 27 توصیه می گردد.
Background & Objectives: Helicobacter pylori is one of the most common pathogen bacteria in human being. Almost half of the population of the world are infected with this bacteria, and it has been known an important factor in gastrointestinal diseases such as; chronic gastritis, gastric ulcer and gastric cancer. Interleukin-27 is a pro-inflammatory cytokine expressed by a novel subset of CD4+ Th cells, and it causes the occurrence and strengthening the inflammatory response. This study was aimed to analysis of association between IL-27 polymorphisms and clinical outcomes due to infection with H. pylori. Materials & Methods: A case-control study has been performed on 434 people 149 patient cases (100 gastritis and 49 ulcerative gastritis), 58 gastritis cases but H. pylori negative and 227 healthy controls. Genomic DNA was extracted and genotypes of IL-27 (-964 A/G) polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Finally the results were compared between these patient and control groups. Results: The frequency of A allele was higher in gastric patients (78.5%) in comparison with the control group (75.6%). However, these differences were not significant. In addition, the distributions of genotypes were not significantly different between the study groups. Conclusion: These results suggest that IL-27 (rs964 A/G) polymorphism gene is not directly involved as a genetic risk factor in the predisposition to H. pylori.
1. Van Doorn LJ, Figueiredo C, Sanna R, Pena S, Midolo P, Ng EK, Atherton JC, Blaser MJ, Quint WG. Expanding allelic diversity of Helicobacter pylorivac A. J Clin Microbiol. 1998; 36(9): 2597-2603.
2. Blaser MJ. Role of vacA and the cagA locus of Helicobacter pylori in human disease. Aliment Pharmacol Ther. 1996; 1: 73-77.
3. Mahan KL, Escott-Stump S. Krause’s food, nutrition & diet therapy. 11th ed. Philadelphia, United States of America: W.B., Saunders. 2004. pp: 692-693.
4. Alborzi A, Soltani J, Pourabbas B, Oboodi B, Haghighat M, Hayati M, Rashidi M. Prevalence of Helicobacter pylori infection in children (south of Iran). Diagn Microbio Infect Dis. 2006; 54 (4): 259-261.
5. Mahram M, Ahmadi F. Seroprevalence of Helicobacter pylori infection among 7–9 year old children in Zanjan. J Res Med Sci. 2006; 5(2): 297-301. [In Persian]
6. Malekzadeh R, Sotoudeh M, Derakhshan MH, Mikaeli J, Yazdanbod A, Merat S, Yoonessi A, Tavangar M, Abedi BA, Sotoudehmanesh R, Pourshams A, Asgari AA, Doulatshahi S, Alizadeh BZ, Arshi S, Madjidpoor A, Mir Moomen S, Fleischer DE. Prevalence of gastric precancerous lesions in Ardabil, a high incidence province for gastric adenocarcinoma in the northwest of Iran. J Clin Pathol. 2004; 57(1): 37-42.
7. Murray LJ, Bamford KB, O’Reilly DP, McCrum EE, Evans AE. Helicobacter pylori infection: relation with cardiovassular risk factors, ischaemic heart disease, and social class. Br Heart J. 1995; 74(5): 497-501.
8. Patel P, Mendall MA, Carrington D, Strachan DP, Leatham E, Molineaux N, Levy J, Blakeston C, Seymour CA, Camm AJ. Association of Helicobacter pylori and Clamydia pneumonia infections with coronary disease and cardiovascular risk factor. BMJ. 1995; 311(7011): 711-714.
9. Li S, You WJ, Zhang JC, Zhou Q, Shi HZ. Immune regulation of interleukin-27 in malignant pleural effusion. Chin Med J (Engl). 2015; 20; 128(14): 1932-1941.
10. Peek RM, Crabtree JE. Helicobacter infection and gastric neoplasia. J Pathol. 2006; 208: 233-248.
11. Shamsdin SA, Alborzi A, Rasouli M, Hosseini MK, Bagheri Lankrani K, Kalani M. Alterations in Th17 and the respective cytokine levels in Helicobacter pylori-Induced stomach diseases. Helicobacter. 2015; 20(6): 460-475.
12. Myung DS ,Lee WS ,Park YL ,Kim N ,Oh HH ,Kim MY ,Oak CY ,Chung CY ,Park HC ,Kim JS ,Cho SB ,Kweon SS ,Joo YE .Association between interleukin-18gene polymorphism and Helicobacter pylori infection in the Korean population. Sci Rep. 2015; 5: 11535.
13. Zhou B, Zhang P, Tang T, Liao H, Zhang K, Pu Y, Chen P, Song Y, Zhang L. Polymorphisms and plasma levels of IL-27: impact on genetic susceptibility and clinical outcome of bladder cancer. BMC Cancer. 2015; 15: 433.
14. Sugimoto M, Yamaoka Y, Furuta T. Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer. World J Gastroenterol. 2010; 16 (10): 1188-1200.
15. Ohyauchi M, Imatani A, Yonechi M, Asano N, Miura A, Iijima K, Koike T, Sekine H, Ohara S, Shimosegawa T. The polymorphism interleukin 8-251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population. Gut. 2005; 54(3): 330-335.
16. Ramis IB, Vianna JS, Concalves CV, von Groll A, Dellagostin OA, da Silva PE. Polymorphisms of IL-6, IL-8 and IL-10 genes and the risk of gastric pathology in patients infected with Helicobacter pylori. J Microbiol Immunol Infect. 2015. pii: S1684-1182(15) 00721-5.
17. Akcil G, Dogan I, Cengiz M, Engin ED, Dogan M, Unal S, Cırak MY, Dursun A. The role of interleukin-1 gene polymorphisms and Helicobacter pylori in gastroesophageal reflux disease.Turk J Gastroenterol. 2014; 25(l): 81-85.
18. Pu Y, Chen P, Zhou B, Zhang P, Wang Y, Song Y, Zhang L. Association between polymorphisms in IL-27 gene and renal cell carcinoma. Biomarkers. 2015; 20(3): 202-205.
19. Nematollahi Z, Hadinedoushan H, Aflatoonian A Eslami G, Ghasemi N. The association between single nucleotide polymorphism in interleukin-27 gene and recurrent pregnancy loss in Iranian women. Iran J Reprod Med. 2015; 13(4): 209-214.
20. Wang Z, Wang L, Zhou J, Zhong J. Association of IL-27 gene three polymorphisms with Crohn’s disease susceptibility in a Chinese Han population. Int J Clin Exp Pathol. 2014; 7(12): 8952-8957.
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1. Van Doorn LJ, Figueiredo C, Sanna R, Pena S, Midolo P, Ng EK, Atherton JC, Blaser MJ, Quint WG. Expanding allelic diversity of Helicobacter pylorivac A. J Clin Microbiol. 1998; 36(9): 2597-2603.
2. Blaser MJ. Role of vacA and the cagA locus of Helicobacter pylori in human disease. Aliment Pharmacol Ther. 1996; 1: 73-77.
3. Mahan KL, Escott-Stump S. Krause’s food, nutrition & diet therapy. 11th ed. Philadelphia, United States of America: W.B., Saunders. 2004. pp: 692-693.
4. Alborzi A, Soltani J, Pourabbas B, Oboodi B, Haghighat M, Hayati M, Rashidi M. Prevalence of Helicobacter pylori infection in children (south of Iran). Diagn Microbio Infect Dis. 2006; 54 (4): 259-261.
5. Mahram M, Ahmadi F. Seroprevalence of Helicobacter pylori infection among 7–9 year old children in Zanjan. J Res Med Sci. 2006; 5(2): 297-301. [In Persian]
6. Malekzadeh R, Sotoudeh M, Derakhshan MH, Mikaeli J, Yazdanbod A, Merat S, Yoonessi A, Tavangar M, Abedi BA, Sotoudehmanesh R, Pourshams A, Asgari AA, Doulatshahi S, Alizadeh BZ, Arshi S, Madjidpoor A, Mir Moomen S, Fleischer DE. Prevalence of gastric precancerous lesions in Ardabil, a high incidence province for gastric adenocarcinoma in the northwest of Iran. J Clin Pathol. 2004; 57(1): 37-42.
7. Murray LJ, Bamford KB, O’Reilly DP, McCrum EE, Evans AE. Helicobacter pylori infection: relation with cardiovassular risk factors, ischaemic heart disease, and social class. Br Heart J. 1995; 74(5): 497-501.
8. Patel P, Mendall MA, Carrington D, Strachan DP, Leatham E, Molineaux N, Levy J, Blakeston C, Seymour CA, Camm AJ. Association of Helicobacter pylori and Clamydia pneumonia infections with coronary disease and cardiovascular risk factor. BMJ. 1995; 311(7011): 711-714.
9. Li S, You WJ, Zhang JC, Zhou Q, Shi HZ. Immune regulation of interleukin-27 in malignant pleural effusion. Chin Med J (Engl). 2015; 20; 128(14): 1932-1941.
10. Peek RM, Crabtree JE. Helicobacter infection and gastric neoplasia. J Pathol. 2006; 208: 233-248.
11. Shamsdin SA, Alborzi A, Rasouli M, Hosseini MK, Bagheri Lankrani K, Kalani M. Alterations in Th17 and the respective cytokine levels in Helicobacter pylori-Induced stomach diseases. Helicobacter. 2015; 20(6): 460-475.
12. Myung DS ,Lee WS ,Park YL ,Kim N ,Oh HH ,Kim MY ,Oak CY ,Chung CY ,Park HC ,Kim JS ,Cho SB ,Kweon SS ,Joo YE .Association between interleukin-18gene polymorphism and Helicobacter pylori infection in the Korean population. Sci Rep. 2015; 5: 11535.
13. Zhou B, Zhang P, Tang T, Liao H, Zhang K, Pu Y, Chen P, Song Y, Zhang L. Polymorphisms and plasma levels of IL-27: impact on genetic susceptibility and clinical outcome of bladder cancer. BMC Cancer. 2015; 15: 433.
14. Sugimoto M, Yamaoka Y, Furuta T. Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer. World J Gastroenterol. 2010; 16 (10): 1188-1200.
15. Ohyauchi M, Imatani A, Yonechi M, Asano N, Miura A, Iijima K, Koike T, Sekine H, Ohara S, Shimosegawa T. The polymorphism interleukin 8-251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population. Gut. 2005; 54(3): 330-335.
16. Ramis IB, Vianna JS, Concalves CV, von Groll A, Dellagostin OA, da Silva PE. Polymorphisms of IL-6, IL-8 and IL-10 genes and the risk of gastric pathology in patients infected with Helicobacter pylori. J Microbiol Immunol Infect. 2015. pii: S1684-1182(15) 00721-5.
17. Akcil G, Dogan I, Cengiz M, Engin ED, Dogan M, Unal S, Cırak MY, Dursun A. The role of interleukin-1 gene polymorphisms and Helicobacter pylori in gastroesophageal reflux disease.Turk J Gastroenterol. 2014; 25(l): 81-85.
18. Pu Y, Chen P, Zhou B, Zhang P, Wang Y, Song Y, Zhang L. Association between polymorphisms in IL-27 gene and renal cell carcinoma. Biomarkers. 2015; 20(3): 202-205.
19. Nematollahi Z, Hadinedoushan H, Aflatoonian A Eslami G, Ghasemi N. The association between single nucleotide polymorphism in interleukin-27 gene and recurrent pregnancy loss in Iranian women. Iran J Reprod Med. 2015; 13(4): 209-214.
20. Wang Z, Wang L, Zhou J, Zhong J. Association of IL-27 gene three polymorphisms with Crohn’s disease susceptibility in a Chinese Han population. Int J Clin Exp Pathol. 2014; 7(12): 8952-8957.