臺灣博碩士論文加值系統

幽門螺旋桿菌Helocobacter pylori (H. pylori)感染消化性潰瘍的產生有關。H. pylori的感染會引起宿主的免疫反應，然而免疫反應卻無法完全清除H. pylori，反而造成宿主的細胞受損。H. pylori感染後的先天性免疫反應之一，是細菌的peptidoglycan經由type IV secretion system注入宿主細胞，被NOD1 (nucleotide-biding oligomerization domain-containing protein 1)辨識之後直接活化NF-κB，誘導胃上皮細胞分泌IL-8 (interleukin 8)。曾有研究發現NOD1 G796A和IL-8 -251 A/T的多型性會增加十二指腸潰瘍的風險，但另外的研究卻指出IL-8 -251 A/T的多型性與胃潰瘍、胃癌有關，與十二指腸潰瘍不相關。本研究的目的是了解國人NOD1 G796A以及IL-8 -251 A/T多型性與H. pylori引起之胃潰瘍和十二指腸潰瘍的相關性。本研究共收集146例胃鏡快速尿素酶檢查的檢體，利用PCR restriction fragment length polymorphism，TaqMan® SNP genotyping assays (real-time PCR)，multilocus sequence typing的方法測定宿主的NOD1 G796A以及IL-8 -251 A/T多型性。統計的結果發現研究對象中，胃潰瘍的發生與年齡有相關性，不具有性別差異；十二指腸潰瘍的發生與H. pylori感染以及性別有關，男性的罹患機率較高。H. pylori感染率沒有性別差異。基因型分析的部份，本研究發現NOD1 G796A多型性為GA或AA，IL-8 -251 T/A多型性為TA或AA時，罹患十二指腸潰瘍與H. pylori的感染有顯著相關，此相關性主要來自於男性族群。H. pylori感染且宿主基因型為NOD1 A allele時，得到十二指腸潰瘍的機率明顯高於沒有感染的GG同型合子。沒有H. pylori感染的人，即使基因型不同罹患十二指腸潰瘍的機率是沒有差異的。由此推測，具有NOD1 A allele的人感染H. pylori之後如果積極進行H. pylori的除菌治療，其罹患十二指腸潰瘍的風險應可明顯降低。然而不論病人屬於哪一種基因型，H. pylori感染都與胃潰瘍都沒有相關性。胃潰瘍的產生在本研究中與H. pylori感染、NOD1、IL-8多型性都沒有相關性，過去有學者認為H. pylori在胃內分布的位置以及胃酸分泌量將會影響胃潰瘍或十二指腸的形成，這是未來需要進一步證實的部份。

Background: H. pylori - induced inflammation is central to the pathogenesis of all H. pylori - associated diseases. The type IV secretion system of H. pylori delivers peptidoglycan into the host cells, which can then be sensed by the intracellular receptor NOD1 (nucleotide-biding oligomerization domain-containing protein 1), leading to NF-κB activation and consequent IL-8 (interleukin 8) production. It had been reported NOD1 G796A and IL-8 -251 A/T polymorphism were important in H. pylori - induced peptic ulcer. However, the results were inconclusive. The aim of this study was to evaluate the role of NOD1 G796A and IL-8 -251 A/T genetic polymorphism in the development of H. pylori -induced peptic ulcer diseases in Taiwan.
Materials and Methods: 146 patients with endoscope and CLO test (Campylobacter like organism test) were enrolled in the study. NOD1 G796A and IL-8 -251 A/T polymorphism were typed by PCR restriction fragment length polymorphism, TaqMan® SNP genotyping assays (real-time PCR) and multilocus sequence typing.
Results: Old age was significantly associated with gastric ulcer in our study population. Duodenal ulcer was associated with H. pylori infection and gender. The prevalence of duodenal ulcer was higher in male. The H. pylori infection rate was similar in male and in female. Male NOD1 796A carriers and male IL-8 -251A carriers significantly had higher risk of H. pylori-induced duodenal ulcer. Since the genotype distribution was similar in H. pylori-infected male and female, polymorphism and gender may be independent factors of H. pylori-induced duodenal ulcer. There was no association between the polymorphism and H. pylori-induced gastric ulcer.
Conclusion: NOD1 796A carriers and IL-8 -251A carriers significantly had higher risk of H. pylori-induced duodenal ulcer in male. However, it still needs further studies to clarify whether genotype or gender-related- factor plays a major role of H. pylori-induced duodenal ulcer in advance.

壹、 縮寫檢索表•••••••••••••••••••••••••••••••••2
貳、 中文摘要•••••••••••••••••••••••••••••••••••4
參、 英文摘要•••••••••••••••••••••••••••••••••••6
肆、 緒論••••••••••••••••••••••••••••••••••••••8
伍、 研究動機••••••••••••••••••••••••••••••••••30
陸、 實驗材料與方法•••••••••••••••••••••••••••••31
柒、 實驗結果••••••••••••••••••••••••••••••••••36
捌、 討論•••••••••••••••••••••••••••••••••••••41
玖、 參考文獻••••••••••••••••••••••••••••••••••49
壹拾、 圖表與說明••••••••••••••••••••••••••••••••58

1.Lin, J.-T. (2002) Formosan J Med 6, 859-862
2.Blaser, M. J., and Atherton, J. C. (2004) The Journal of Clinical Investigation 113, 321-333
3.Wang, W.-M. (2002) Formosan J Med 6, 866-875
4.Ernst, P. B., Peura, D. A., and Crowe, S. E. (2006) Gastroenterology 130, 188-206
5.Suerbaum, S., and Michetti, P. (2002) The New Englane journal of medicine 347, 1175-1186
6.Wang, J.-T. (2002) Formosan J Med 6, 863-865
7.Lin, C.-W., Chang, Y.-S., Wu, S.-C., and Cheng, K.-S. (1998) Japanese journal of medical science & biology 51, 13-23
8.Sheu, B.-S., Sheu, S.-M., Yang, H.-B., Huang, A.-H., and Wu, J.-J. (2002) Gut 52, 927-934
9.Ouburg, S., Crusius, J. B. A., Klinkenberg-Knol, E. C., Mulder, C. J. J., Pena, A. S., and Morre, S. A. (2005) European Journal of Gastroenterology & Hepatology 17, 1213-1223
10.Konturek, S., Konturek, P., T, B., Konturek, J., and Pawlik, W. (2005) Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 56, 507-530
11.Marshall, B. (1989) Campylobacter pylori in gastritis and peptic ulcer disease. New York: Igaku Shoin, 7-23
12.Talley, N., Zinsmeister, A., Weaver, A., DiMagno, E., Carpenter, H., Perez-Perez, G., and Blaser, M. (1991) Journal of the national cancer institute 83, 1734-1739
13.Parsonnet, J., Friedman, G., Vandersteen, D., Chang, Y., Vogelman, J., Orentreich, N., and Sibley, R. (1991) The New Englane journal of medicine 325, 1127-1131
14.Parsonnet, J., Vandersteen, D., Goates, J., Sibley, R., Pritikin, J., and Chang, Y. (1991) Journal of the national cancer institute 83, 640-643
15.IARC. (1994) IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, International Agency for Research on Cancer 61, 1-241
16.Tomb, J., White, O., Kerlavage, A., Clayton, R., Sutton, G., and Fleischmann, R. (1997) Nature 388, 515-516
17.Alm, R., Ling, L., and moir, D. (1999) Nature 397, 176-180
18.Xu, Q., Morgan, R., Roberts, R., and Blaser, M. (2000) Proceedings of the National Academy of Sciences of the United States of America 97, 9671-9676
19.Webb, G., and Blaser, M. (2004) Proceedings of the National Academy of Sciences of the United States of America 99, 3135-3140
20.Kersulyte, D., Chalkauskas, H., and Berg, D. (1999) Molecular microbiology 31, 31-43
21.Muotiala, A., Helander, I., Pyhälä, L., Kosunen, T., and Moran, A. (1992) Infection and immunity 60, 1714-1716
22.Moran, A., Knirel, Y., Senchenkova, S., Widmalm, G., Hynes, S., and Jansson, P. (2002) Journal of biological chemistry 277, 5785-5795
23.Gewirtz, A., Yu, Y., Krishna, U., Israel, D., Lyons, S., and Peek, R. J. (2004) The Journal of infectious diseases 189, 1914-1920
24.Amieva, M. R., and EL-Omar, E. M. (2008) Gastroenterology 134, 306-323
25.Croxen, M., Sisson, G., Melano, R., and Hoffman, P. (2006) Journal of bacteriology 188, 2656-2665
26.Ilver, D., Arnqvist, A., Ogren, J., Frick, I., Kersulyte, D., Incecik, E., Berg, D., Covacci, A., Engstrand, L., and Borén, T. (1998) Science 279, 373-377
27.Mahdavi, J., Sondén, B., Hurtig, M., Olfat, F., Forsberg, L., Roche, N., Angstrom, J., Larsson, T., Teneberg, S., Karlsson, K., Altraja, S., Wadström, T., Kersulyte, D., Berg, D., Dubois, A., Petersson, C., Magnusson, K., Norberg, T., Lindh, F., Lundskog, B., Arnqvist, A., Hammarström, L., and Borén, T. (2002) Science 297, 573-578
28.Dossumbekova, A., Prinz, C., Gerhard, M., Brenner, L., Backert, S., Kusters, J., Schmid, R., and Rad, R. (2006) Gut 55, 1360-1361
29.Petersson, C., Forsberg, M., Aspholm, M., Olfat, F., Forslund, T., Borén, T., and Magnusson, K. (2006) Medical microbiology and immunology 195, 195-206
30.Ernst, P., and Gold, B. (2000) Palo Alto, CA: Annual Reviews 54th ed., 615-640
31.Suerbaum, S., and Michetti, P. (2002) The New Englane journal of medicine 347, 1175-1186
32.Frenck, R. J., and J, J. C. (2003) Microbes and infection / Institut Pasteur 5, 705-713
33.Snaith, A., and El-Omar, E. (2008) Expert review of gastroenterology & hepatology 2, 577-585
34.Fox, J., and Wang, T. (2001) The New Englane journal of medicine 345, 829-832
35.Bhan, M., Bahl, R., Sazawal, S., Sinha, A., Kumar, R., Mahalanabis, D., and Clemens, J. (2002) The Journal of infectious diseases 186, 1857-1860
36.Perry, S., Sanchez, L., Yang, S., Haggerty, T., Hurst, P., and Parsonnet, J. (2004) The Journal of infectious diseases 190, 303-310
37.Blaser, M. J. (2008) Cancer prevention research (Philadelphia, Pa.) 1, 308-311
38.Nomura, A., Pérez-Pérez, G., Lee, J., Stemmermann, G., and Blaser, M. (2002) American journal of epidemiology 155, 1054-1059
39.Huang, J., Zheng, G., Sumanac, K., Irvine, E., and Hunt, R. (2003) Gastroenterology 125, 1636-1644
40.Naumann, M., and Crabtree, J. (2004) Trends in Microbiology 12, 29-36
41.Pérez-Pérez, G., Bhat, N., Gaensbauer, J., Fraser, A., Taylor, D., Kuipers, E., Zhang, L., You, W., and Blaser, M. (1997) International journal of cancer 72, 453-456
42.Higashi, H., Tsutsumi, R., Fujita, A., Yamazaki, S., Asaka, M., Azuma, T., and Hatakeyama, M. (2002) Proceedings of the National Academy of Sciences of the United States of America 99, 14428-14433
43.Backert, S., Moese, S., Selbach, M., Brinkmann, V., and Meyer, T. (2001) Molecular microbiology 42, 631-644
44.Moese, S., Selbach, M., Kwok, T., Brinkmann, V., König, W., Meyer, T., and Backert, S. (2004) Infection and immunity 72, 3646-3649
45.Churin, Y., Al-Ghoul, L., Kepp, O., Meyer, T., Birchmeier, W., and Naumann, M. (2003) The journal of biological chemistry 161, 249-255
46.Meyer-ter-Vehn, T., Covacci, A., Kist, M., and Pahl, H. (2000) The journal of biological chemistry 275, 16064-16072
47.Tsutsumi, R., Higashi, H., Higuchi, M., Okada, M., and Hatakeyama, M. (2003) The journal of biological chemistry 278, 3664-3670
48.Moss, S., Sordillo, E., Abdalla, A., Makarov, V., Hanzely, Z., Pérez-Pérez, G., Blaser, M., and Holt, P. (2001) Cancer Research 61, 1406-1411
49.Peek, R. J., Moss, S., Tham, K., Pérez-Pérez, G., Wang, S., Miller, G., Atherton, J., Holt, P., and Blaser, M. (1997) Journal of the national cancer institute 89, 863-868
50.Chang, Y., Wu, M., Lin, J., Pestell, R., Blaser, M., and Chen, C. (2006) Cellular Microbiology 8, 1740-1752
51.Yokoyama, K., Higashi, H., Ishikawa, S., Fujii, Y., Kondo, S., Kato, H., Azuma, T., Wada, A., Hirayama, T., Aburatani, H., and Hatakeyama, M. (2005) Proceedings of the National Academy of Sciences of the United States of America 102, 9661-9666
52.Amieva, M., Vogelmann, R., Covacci, A., Tompkins, L., Nelson, W., and Falkow, S. (2003) Science 300, 1430-1434
53.Higashi, H., Nakaya, A., Tsutsumi, R., Yokoyama, K., Fujii, Y., Ishikawa, S., Higuchi, M., Takahashi, A., Kurashima, Y., Teishikata, Y., Tanaka, S., Azuma, T., and Hatakeyama, M. (2004) The journal of biological chemistry 279, 17205-17216
54.Hirata, Y., Maeda, S., Mitsuno, Y., Tateishi, K., Yanai, A., Akanuma, M., Yoshida, H., Kawabe, T., Shiratori, Y., and Omata, M. (2002) Gastroenterology 123, 1962-1971
55.El-Etr, S., Mueller, A., Tompkins, L., Falkow, S., and Merrell, D. (2004) The Journal of infectious diseases 190, 1516-1523
56.Cover, T. (1996) Molecular microbiology 20, 241-246
57.Atherton, J., Cao, P., Peek, R., Tummuru, M., Blaser, M., and Cover, T. (1995) The journal of biological chemistry 270, 17771-17777
58.Yamazaki, S., Yamakawa, A., Okuda, T., Ohtani, M., Suto, H., Ito, Y., Yamazaki, Y., Keida, Y., Higashi, H., Hatakeyama, M., and Azuma, T. (2005) Journal of clinical microbiology 43, 3906-3916
59.Molinari, M., Salio, M., Galli, C., Norais, N., Rappuoli, R., Lanzavecchia, A., and Montecucco, C. (1998) The Journal of Experimental Medicine 187, 135-140
60.Willhite, D., and Blanke, S. (2004) Cellular Microbiology 6, 143-154
61.Yamasaki, E., Wada, A., Kumatori, A., Nakagawa, I., Funao, J., Nakayama, M., Hisatsune, J., Kimura, M., Moss, J., and Hirayama, T. (2006) Journal of biological chemistry 281, 11250-11259
62.Fujikawa, A., Shirasaka, D., Yamamoto, S., Ota, H., Yahiro, K., Fukada, M., Shintani, T., Wada, A., Aoyama, N., Hirayama, T., Fukamachi, H., and Noda, M. (2003) Nature Genetics 33, 375-381
63.Gebert, B., Fischer, W., Weiss, E., Hoffmann, R., and Haas, R. (2003) Science 301, 1099-1102
64.Lindén, S., Nordman, H., Hedenbro, J., Hurtig, M., Borén, T., and Carlstedt, I. (2002) Gastroenterology 123, 1923-1930
65.Rad, R., Gerhard, M., Lang, R., Schöniger, M., Rösch, T., Schepp, W., Becker, I., Wagner, H., and Prinz, C. (2002) Journal of Immunology 168, 3033-3041
66.Gerhard, M., Lehn, N., Neumayer, N., Borén, T., Rad, R., Schepp, W., Miehlke, S., Classen, M., and Prinz, C. (1999) Proceedings of the National Academy of Sciences of the United States of America 96, 12778-12883
67.Aspholm-Hurtig, M., Dailide, G., Lahmann, M., Kalia, A., lver, D., Roche, N., Vikström, S., Sjöström, R., Lindén, S., Bäckström, A., Lundberg, C., Arnqvist, A., Mahdavi, J., Nilsson, U., Velapatiño, B., Gilman, R., Gerhard, M., Alarcon, T., López-Brea, M., Nakazawa, T., Fox, J., Correa, P., Dominguez-Bello, M., Perez-Perez, G., Blaser, M., Normark, S., Carlstedt, I., Oscarson, S., Teneberg, S., Berg, D., and Borén, T. (2004) Science 305, 519-522
68.Ernst, P., Ryan, K., and Goldberg, J. (2003) In: Hunt RH, Tytgat GNJ, eds. Helicobacter pylori: basic mechanisms to clinical cure 2002. London, England: Kluwer, 73-82
69.Mentis, A., Blackwell, C., Weir, D., Spiliadis, C., Dailianas, A., and Skandalis, N. (1991) Epidemiology and Infection 106, 221-229
70.Mizushima, T., Sugiyama, T., Komatsu, Y., Ishizuka, J., Kato, M., and Asaka, M. (2001) Journal of clinical microbiology 39, 2463-2465
71.Taylor, D., Rasko, D., Sherburne, R., Ho, C., and Jewell, L. (1998) Gastroenterology 115, 1113-1122
72.Yamaoka, Y., Kwon, D., and Graham, D. (2000) Proceedings of the National Academy of Sciences of the United States of America 97, 7533-7538
73.Yamaoka, Y., Kikuchi, S., el-Zimaity, H., Gutierrez, O., Osato, M., and Graham, D. (2002) Gastroenterology 123, 414-424
74.Kidd, M., Peek, R., Lastovica, A., Israel, D., Kummer, A., and Louw, J. (2001) Gut 49, 629-635
75.Xu, Q., and Blaser, M. (2001) Journal of bacteriology 183, 3875-3884
76.Heithoff, D., Sinsheimer, R., Low, D., and Mahan, M. (1999) Science 284, 967-970
77.Atherton, J., Tham, K., Peek, R. J., Cover, T., and Blaser, M. (1996) The Journal of infectious diseases 174, 552-556
78.Hamlet, A., and Olbe, L. (1996) Gastroenterology 111, 391-400
79.Khulusi, S., Badve, S., Patel, P., Lloyd, R., Marrero, J., Finlayson, C., Mendall, M., and Northfield, T. (1996) Gastroenterology 110, 452-458
80.Zanten, S. V., Dixon, M., and Lee, A. (1999) Gastroenterology 116, 1217-1229
81.Macarthur, M., Hold, G., and El-Omar, E. (2004) American journal of physiology. Gastrointestinal and liver physiology 286, G515-G520
82.May, M. J., and Ghosh, S. (1997) Seminars in Cancer Biology 8, 63-73
83.Hamajima, N., Naito, M., Kondo, T., and Goto, Y. (2006) Cancer Science 97, 1129-1138
84.Rutault, K., Hazzalin, C. A., and Mahadevan, L. C. (2001) Journal of biological chemistry 276, 6666-6674
85.Medzhitov, R. (2001) Nature Reviews Immunology 1, 135-145
86.Evans, T. J. (2009) Future Microbiology 4, 65-75
87.Ishihara, S., Rumi, M., Kadowaki, Y., Ortega-Cava, C., Yuki, T., Yoshino, N., Miyaoka, Y., Kazumori, H., Ishimura, N., Amano, Y., and Kinoshita, Y. (2004) Journal of Immunology 173, 1406-1416
88.Smith, M. J., Mitchell, A., Li, G., Ding, S., Fitzmaurice, A., Ryan, K., Crowe, S., and Goldberg, J. (2003) The journal of biological chemistry 278, 32552-32560
89.Mandell, L., Moran, A., Cocchiarella, A., Houghton, J., Taylor, N., Fox, J., Wang, T., and Kurt-Jones, E. (2004) Infection and Immunity 72, 6446-6454
90.Wu, M., Cheng, T., Shun, C., Lin, M., Chen, L., and Lin, J. (2006) Hepatogastroenterology 53, 807-810
91.Takeda, K., and Akira, S. (2005) International Immunology 17, 1-14
92.Athman, R., and Philpott, D. (2004) Current Opinion in microbiology 7, 25-32
93.Viala, J., Chaput, C., Boneca, I., Cardona, A., Girardin, S., Moran, A., Athman, R., Mémet, S., Huerre, M., Coyle, A., DiStefano, P., Sansonetti, P., Labigne, A., Bertin, J., Philpott, D., and Ferrero, R. (2004) Nature Immunology 5, 1166-1174
94.Girardin, S., Boneca, I., Carneiro, L., Antignac, A., Jéhanno, M., Viala, J., Tedin, K., Taha, M., Labigne, A., Zähringer, U., Coyle, A., DiStefano, P., Bertin, J., Sansonetti, P., and Philpott, D. (2003) Science 300, 1584-1587
95.Strober, W., Murray, P. J., Kitani, A., and Watanabe, T. (2006) Nature Reviews Immunology 6, 9-20
96.Brink, G. v. D., Kate, F. t., Ponsioen, C., Rive, M., Tytgat, G., Deventer, S. v., and Peppelenbosch, M. (2000) Journal of Immunology 164, 3353-3359
97.Isomoto, H., Mizuta, Y., Miyazaki, M., Takeshima, F., Omagari, K., Murase, K., Nishiyama, T., Inoue, K., Murata, I., and Kohno, S. (2000) American Journal of Gastroenterology 95, 2768-2776
98.Ding, S., O''Hara, A., Denning, T., Dirden-Kramer, B., Mifflin, R., Reyes, V., Ryan, K., Elliott, S., Izumi, T., Boldogh, I., Mitra, S., Ernst, P., and Crowe, S. (2004) Gastroenterology 127, 845-858
99.O''Hara, A., Bhattacharyya, A., Mifflin, R., Smith, M., Ryan, K., Scott, K., Naganuma, M., Casola, A., Izumi, T., Mitra, S., Ernst, P., and Crowe, S. (2006) Journal of Immunology 177, 7990-7999
100.Maeda, S., Yoshida, H., Ogura, K., Mitsuno, Y., Hirata, Y., Yamaji, Y., Akanuma, M., Shiratori, Y., and Omata, M. (2000) Gastroenterology 199, 97-108
101.Peek, R. J. (2001) American Journal of Physiology. Gastrointestinal and Liver Physiology 280, G525-G530
102.Yamaoka, Y., Kudo, T., Lu, H., Casola, A., Brasier, A., and Graham, D. (2004) Gastroenterology 126, 1030-1043
103.Bamford, K., Fan, X., Crowe, S., Leary, J., Gourley, W., Luthra, G., Brooks, E., Graham, D., Reyes, V., and Ernst, P. (1998) Gastroenterology 114, 482-492
104.Bergman, M., Engering, A., Smits, H., Vliet, S. v., Bodegraven, A. v., Wirth, H., Kapsenberg, M., Vandenbroucke-Grauls, C., Kooyk, Y. v., and Appelmelk, B. (2004) The Journal of Experimental Medicine 200, 979-990
105.Sebkova, L., Pellicanò, A., Monteleone, G., Grazioli, B., Guarnieri, G., Imeneo, M., Pallone, F., and Luzza, F. (2004) Infection and immunity 72, 5019-5026
106.Yamori, M., Yoshida, M., Watanabe, T., Shirai, Y., Iizuka, T., Kita, T., and Wakatsuki, Y. (2004) Biochemical and Biophysical Research Communications 316, 1015-1021
107.Wang, J., Fan, X., Lindholm, C., Bennett, M., O''Connoll, J., Shanahan, F., Brooks, E., Reyes, V., and Ernst, P. (2000) Infection and immunity 68, 4303-4311
108.Fan, X., Gunasena, H., Cheng, Z., Espejo, R., Crowe, S., Ernst, P., and Reyes, V. (2000) Journal of Immunology 165, 1918-1924
109.Beswick, E., Das, S., Pinchuk, I., Adegboyega, P., Suarez, G., Yamaoka, Y., and Reyes, V. (2005) Journal of Immunology 175, 171-176
110.El-Omar, E., Carrington, M., Chow, W., McColl, K., Bream, J., Young, H., Herrera, J., Lissowska, J., Yuan, C., Rothman, N., Lanyon, G., Martin, M., Fraumeni, J. J., and Rabkin, C. (2000) Nature 404, 398-402
111.Imatani, A., Ohara, S., Yonechi, M., Ohyauchi, M., and Shimosegawa, T. (2004) Nippon Rinsho. Japansese Journal of Clinical Medicine 62, 442-447
112.Hsu, P., Li, C., Tseng, H., Lai, K., Hsu, P., Lo, G., Lo, C., Yeh, J., Ger, L., Hsiao, M., Yamaoka, Y., Hwang, I., and Chen, A. (2004) Helicobacter 9, 605-613
113.Furuta, T., El-Omar, E., Xiao, F., Shirai, N., Takashima, M., and Sugimura, H. (2002) Gastroenterology 123, 92-105
114.El-Omar, E., Rabkin, C., Gammon, M., Vaughan, T., Risch, H., Schoenberg, J., Stanford, J., Mayne, S., Goedert, J., Blot, W., Fraumeni, J. J., and Chow, W. (2003) Gastroenterology 124, 1193-1201
115.Ohyauchi, M., Imatani, A., Yonechi, M., Asano, N., Miura, A., Iijima, K., Koike, T., Sekine, H., Ohara, S., and Shimosegawa, T. (2005) Gut 54, 330-335
116.Fey, M., and Tobler, A. (1993) Human Genetics 91, 298
117.Hamajima, N., Katsuda, N., Matsuo, K., Saito, T., Hirose, K., Inoue, M., Zaki, T., Tajima, K., and Tominaga, S. (2003) Helicobacter 8, 105-110
118.Smith, M. G., Hold, G. L., Rabkin, C. S., Chow, W.-H., Kenneth, E., McColl, K., Perez-Perez, G., Ashley, M., and M, E.-O. E. (2004) Gastroenterology 126, A23
119.Heinzmann, A., Ahlert, I., Kurz, T., Berner, R., and Deichmann, K. (2004) The journal of allergy and clinical immunology 114, 671-676
120.Kuyl, A. v. d., Polstra, A., Weverling, G., Zorgdrager, F., Burg, R. v. d., and Cornelissen, M. (2004) AIDS 18, 1206-1208
121.Ross, O., O''Neill, C., Rea, I., Lynch, T., Gosal, D., Wallace, A., Curran, M., Middleton, D., and Gibson, J. (2004) Human Immunology 65, 340-346
122.Taguchi, A., Ohmiya, N., Shirai, K., Mabuchi, N., Itoh, A., Hirooka, Y., Niwa, Y., and Goto, H. (2005) Cancer Epidemiology, Biomarkers & Prevention 14, 2487-2493
123.Hysi, P., Kabesch, M., Moffatt, M., Schedel, M., Carr, D., Zhang, Y., Boardman, B., Mutius, E. v., Weiland, S., Leupold, W., Fritzsch, C., Klopp, N., Musk, A., James, A., Nunez, G., Inohara, N., and Cookson, W. (2005) Human Molecular Genetics 14, 935-941
124.McGovern, D., Hysi, P., Ahmad, T., Heel, D. v., Moffatt, M., Carey, A., Cookson, W., and Jewell, D. (2005) Human Molecular Genetics 14, 1245-1250
125.Rosenstiel, P., Hellmig, S., Hampe, J., Ott, S., Till, A., Fischbach, W., Sahly, H., Lucius, R., Fölsch, U. R., Philpott, D., and Schreiber, S. (2006) Cellular Microbiology 8, 1188-1198
126.Hofner, P., Gyulai, Z., Kiss, Z. F., Tiszai, A., Tiszlavicz, L., Tóth, G., Szõke, D., Molnár, B., Lonovics, J., Tulassay, Z., and Mándi, Y. (2007) Helicobacter 12, 124-131
127.Wang, W., Chen, C., Jan, C., Lan, T., Chen, L., Lin, S., and Chien, C. (1990) Journal of The Formosan Medical Association 89, 683-686
128.Shallcross, T., Rathbone, B., Wyatt, J., and Heatley, R. (1990) Alimentary pharmacology & therapeutics 4, 515-522
129.Sanger, F. (1981) Science 214, 1205-1210
130.Aro, P., Storskrubb, T., Ronkainen, J., Bolling-Sternevald, E., Engstrand, L., Vieth, M., Stolte, M., Talley, N. J., and Agreus, L. (2006) American Journal of Epidemiology 163, 1025-1034
131.Fock, K. M., Talley, N., Moayyedi, P., Hunt, R., Azuma, T., Sugano, K., Xiao, S. D., Lam, S. K., Goh, K. L., Chiba, T., Uemura, N., Kim, J. G., Kim, N., Ang, T. L., Mahachai, V., Mitchell, H., Rani, A. A., Liou, J. M., Vilaichone, R.-k., and Sollano, J. (2008) Journal of Gastroenterology and Hepatology 23, 351-365
132.Papatheodoridis, G., Sougioultzis, S., and Archimandritis, A. (2006) Clinical Gastroenterology and Hepatology 4, 130-142
133.Lin, J., Wang, J., Wu, M., Wang, T., Lee, T., and Chen, C. (1994) Scandinavian Journal of Gastroenterology 28, 1067-1072
134.Hull, J., Ackerman, H., Isles, K., Usen, S., Pinder, M., Thomson, A., and Kwiatkowski, D. (2001) American Journal of Human Genetics 69, 413-419
135.Gyulai, Z., lausz, G., Tiszai, A., Lénárt, Z., Kása, I., Lonovics, J., and Mándi, Y. (2004) European cytokine network 15, 353-358