Association Between HLA-DQ Genotypes and Haplotypes vs Helicobacter pylori Infection in an Indonesian Population

  • Zhao, Yang ;
  • Wang, Jingwen ;
  • Tanaka, Tsutomu ;
  • Hosono, Akihiro ;
  • Ando, Ryosuke ;
  • Soeripto, Soeripto ;
  • Triningsih, F.X. Ediati ;
  • Triono, Tegu ;
  • Sumoharjo, Suwignyo ;
  • Astuti, E.Y. Wenny ;
  • Gunawan, Stephanus ;
  • Tokudome, Shinkan
  • Published : 2012.04.30


Background: Helicobacter pylori is an important gastrointestinal pathogen related to the development of not only atrophic gastritis and peptic ulcer, but also gastric cancer. Human leukocyte antigens (HLA) may play particular roles in host immune responses to bacterial antigens. This study aimed to investigate the association between HLA-DQA1 and DQB1 genotypes and haplotypes vs H. pylori infection in an Indonesian population. Methods: We selected 294 healthy participants in Mataram, Lombok Island, Indonesia. H. pylori infection was determined by urea breath test (UBT). We analyzed HLA-DQA1 and DQB1 genotypes by PCR-RFLP and constructed haplotypes of HLA-DQA1 and DQB1 genes. Multiple comparisons were conducted according to the Bonferroni method. Results: The H. pylori infection rate was 11.2% in this Indonesian population. The DQB1*0401 genotype was noted to be associated with a high risk of H. pylori infection, compared with the DQB1*0301 genotype. None of the HLA-DQA1 or DQB1 haplotypes were related to the risk of H. pylori infection. Conclusions: The study suggests that HLADQB1 genes play important roles in H. pylori infection, but there was no statistically significant association between HLA-DQA1 or DQB1 haplotypes and H.pylori infection in our Lombok Indonesian population.


HLA;DQA1;HLA;DQB1;haplotype;H. pylori;infection;association


  1. Amar A, Rubinstein N, Hacham ZS, et al (1984). Is predisposition to pemphigus vulgaris in jewish patients mediated by HLADw10 and DR4? Tissue Antigens, 23, 17-22.
  2. Asaka M, Kimura T, Kato M, et al (1994). Possible role of Helicobacter pylori infection in early gastric cancer development. Cancer, 73, 2691-4.<2691::AID-CNCR2820731107>3.0.CO;2-2
  3. Azuma T, Ito Y, Miyaji H, et al (1995). Immunogenetic analysis of the human leukocyte antigen DQA1 locus in patients with duodenal ulcer or chronic atrophic gastritis harbouring Helicobacter pylori. Eur J Gastroerol Hepatol, 7, 71-3.
  4. Brown LM (2000). Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev, 22, 283-97.
  5. Brown LM, Thomas TL, Ma JL, et al (2002). Helicobacter pylori infection in rural China: demographic, lifestyle and environmental factors. Int J Epidemiol, 31, 638-45.
  6. Brown P, Breguet G, Smallwood L, et al (1985). Serologic markers of hepatitis A and B in the population of Bali, Indonesia. Am J Trop Med Hyg, 34, 616-9.
  7. Cairncross S (1997). More water: better health. People Planet, 6, 10-1.
  8. Da Cunha SS, Pujades-Rodrjguez M, Barreto ML, et al (2007). Ecological study of socio-economic indicators and prevalence of asthma in school children in urban Brazil. BMC Public Health, 7, 205.
  9. Etoglu G, Betz G, Torregano C (1992). Impact of histocompatibity antigens on pregnancy outcome. Am J Obstet Gynecol, 166, 1364-9.
  10. Fan X, Crowe SE, Behar S, et al (1998). The effect of histocompatibility complex expression on adherence of Helicobacter pylori and induction of apoptosis in gastric epithelial cell: a mechanism for T helper cell type 1-mediated damage. J Exp Med, 187, 1659-69.
  11. Feachem RG, Guy MW, Harrison S, et al (1983). Excreta disposal facilities and intestinal parasitism in urban Africa: preliminary studies in Botswana, Ghana and Zambia. Trans R Soc Trop Med Hyg, 77, 515-21.
  12. Hamajima N, Naito M, Kondo T, et al (2006). Genetic factors involved in the development of Helicobacter pylori-related gastric cancer. Cancer Sci, 97, 1129-38.
  13. Herrera-Goepfere R, Yamamoto-Furusho JK, Onate-Ocana LF et al (2006). Role of the HLA-DQ locus in the development of chronic gastritis and gastric carcinoma in Mexican patients. World J Gastroenterol, 12, 7762-7.
  14. Hill AVS, Allosopp CEM, Kwiatkowski D, et al (1991). Common West African HLA antigens are associated with protection from severe malaria. Nature, 352, 595-600.
  15. Hoang PL, Trong KH, Tran TT, et al (2008). Detection of hepatitis A virus RNV from children patients with acute and fulminant hepatitis of unknown etiology in Vietnam: genomic characterization of Vietnamese HAV strain. Pediatr Int, 50, 624-7.
  16. Honda S, Fujioka T, Tokieda M, et al (1998). Development of Helicobacter pylori-induced gastric carcinoma in Mongolian gerbils. Cancer Res, 58, 4255-9.
  17. Huang YK, Wen GS, Li HL, et al (2005). Possible association between HLA-HRB1 and DQB1 genes frequency and susceptibility or resistance to Helicobacter pylori infection in Kunming Yi ethnic group children. Zhong hua Er Ke Za Zhi, 43, 137-40.
  18. Kaufman JF, Auffray C, Korman AJ, et al (1984). The class II molecules of the human and murine major histocompatibility complex. Cell, 36, 1-13.
  19. Klein PD, Graham DY, Gaillour A, et al (1991). Water source as risk factor for Helicobacter pylori infection Peruvian children. Gastrointestinal Physiology Working G. Lancet, 22, 1503-6.
  20. Ko KP, Park SK, Park B, et al (2010). Isoflavones from phytoestrogens and gastric cancer risk: a nested case-control study within the Korean Multicenter Cancer Cohort. Cancer Epidemiol Biomarkers Prev, 19, 1292-300.
  21. Kusters JG, Van Vliet AH, Kuipers EJ (2006). Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev, 19, 449-90.
  22. Lee JH, Kim N, Chung JI, et al (2008). Long-term followup of Helicobacter pylori serology after eradication and reinfection rate of H. pylori in South Korea. Helicobacter, 13, 288-94.
  23. Liewelyn M, Sriskandan S, Peakman M, et al (2004). HLA class II polymorphisms determine responses to bacterial superantigens. J Immunol, 172, 1719-26.
  24. Maeda M, Murayama N, Ishi H, et al (1989). A simple and rapid method for HLA-DQA1 genotyping by digestion of PCR-amplified DNA with allele-specific restriction endonucleases. Tissue Antigens, 34, 290-8.
  25. Mckeown I, Orr P, Macdonald S, et al. (1999) Helicobacter pylori in the Canadian Arctic: seroprevalence and detection in community water samples. Am J Gastroenterol , 94, 1823-9.
  26. Nguyen BV, Nguyen KG, Phung CD, et al (2006). Prevalence of factors associated with Helicobacter pylori infection in children in the North of Vietnam. Am J Trop Med Hyg, 74, 536-9.
  27. Nomura N, Ota M, Tsuji K, et al (1991). HLA-DQB1 genotyping by a modified PCR-RFLP method combined with groupspecific primers. Tissue Antigens, 38, 53-9.
  28. Nurgalieva ZZ, Conner ME, Opekun AR, et al (2005). B-cell and T-cell immune responses to experimental Helicobacter pylori infection in humans. Infect Immun, 73, 2999-3006.
  29. Ohmori M, Yasunaga S, Maehara Y, et al (1997). DNA typing of HLA class I (HLA-A) and class II genes (HLA-DR, DQ and -DP) in Japanese patients with gastric cancer. Tissue Antigens, 50, 277-82.
  30. Ota M, Seki T, Nomura N, et al (1991). Modified PCR-RFLP method for HLA-DPB1 and DQA1 genotyping. Tissue Antigens, 38, 60-71.
  31. Payami H, Thomson G, Khan MA, et al (1986). Genetics of rheumatoid arthritis. Tissue Antigens, 27,57-63.
  32. Peace DJ, Chen W, Nelson H, et al (1991). T cell recognition of transforming proteins encoded by mucoded by mutated ras proto-oncogenes. J Immunol, 146, 2059-65.
  33. Peek RM, Wirth H-P, Moss SF, et al (2000). Helicobacter pylori alters gastric epithelial cell cycle events and gastric secretion in Mongolian gerbils. Gastroenterology, 118, 48-59.
  34. Rotter J I, Landlaw E M (1984). Measuring the genetic contribution of a single locus to a multilocus disease. Clin Genet, 26, 529-42.
  35. Sette A, Buus S, Colon S, et al (1987). Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells. Nature, 328, 395-9.
  36. Steck T, Van der Ven K, Kwak J (1995). HLA-DQA1 and HLA-DQB1 genotypes in aborted fetuses and couples with recurrent spontaneous abortion. J Reprod Immunol, 29, 95-104.
  37. Teutsch SM, Bennetts BH, Castle M, et al (1996). HLA-DQA1 and DQB1 genotyping by PCR-RFLP, heteroduplex and homoduplex analysis. Eur J Immunogenet, 23, 107-20.
  38. Todd JA, Acha-Orbea H, Bell JI, et al (1988). A molecular basis for MHC class II associated autoimmunity. Science, 240, 1003-9.
  39. Todd JA, Bell JI, McDevitt HO (1987). HLA-$DQ{\beta}$ gene contributes to susceptibility and resistance to insulindependent diabetes mellitus. Nature, 329, 599-604.
  40. Tokudome S, Soeripto, Triningsih FXE, et al.(2005) Rare Helicobacter pylori infection as a factor for the very low stomach cancer incidence in Yogyakarta, Indonesia. Cancer Lett, 219, 57-61.
  41. Tokudome S, Samsuria WD, Soeripto, et al (2005). Helicobacter pylori infection appears essential for stomach carcinogenesis: observations in Semarang, Indonesia. Cancer Sci, 96, 873-5.
  42. Topalian SL, Rivoltini L, Mancini M, et al (1994). Human CD4+T cells specifically recognize a shared melanomaassociated antigen encoded by the tyrosinase gene. Proc Natl Acad Sci, 91, 9461-5.
  43. Uryu N, Maeda M, Ota M, et al (1990). A simple and rapid method for HLA-DRB and -DQB typing by digestion of PCR-amplified DNA with allele specific restriction endonucleases. Tissue Antigens, 35, 20-31.
  44. Veldhuyzen van Zanten SJ, Sherman PM. (1994) Helicobacter pylori infection as a cause of gastritis, duodenal ulcer, gastric cancer and nonulcer dyspepsia, a systematic overview. CMAJ, 150, 177-85.
  45. Wang LL, Tran DB, Lin WX, et al (2004). Association of HLADQA1 loci with Helicobacter pylori infection in children of Guangxi Zhuang, Mulam nationalities, China and Central Jing nationality, Vietnam. Zhong hua Er Ke Za Zhi, 42, 577-80.
  46. Wang XP, Lin QD, Lu, PH, et al (2004). Association of HLA-DQB1 coding region with unexplained recurrent spontaneous abortion. Chin Med J, 117, 492-7.
  47. Yamaoka Y, Orito E, Mizokami M, et al (2002). Helicobacter pylori in North and South America before Columbus. FEBS Lett, 517, 180-4.
  48. Yasui W, Sentani K, Motoshita J, et al (2006) Molecular pathobiology of gastric cancer. Scand J Surg, 95, 225-31.

Cited by

  1. Changes in Median Ages at Death from Selected Cancer Types in Relation to HLA-DRB1/DQB1 vol.15, pp.10, 2014,
  2. Evaluation of the Atlas Helicobacter pylori Stool Antigen Test for Diagnosis of Infection in Adult Patients vol.15, pp.13, 2014,
  3. Virulence Genes of Helicobacter pylori in Gastritis, Peptic Ulcer and Gastric Cancer in Laos vol.15, pp.20, 2014,
  4. Extremely low Helicobacter pylori prevalence in North Sulawesi, Indonesia and identification of a Maori-tribe type strain: a cross sectional study vol.6, pp.1, 2014,
  5. Risk Factors and Prevalence of Helicobacter pylori in Five Largest Islands of Indonesia: A Preliminary Study vol.10, pp.11, 2015,
  6. Identification of Helicobacter pylori infection in symptomatic patients in Surabaya, Indonesia, using five diagnostic tests vol.143, pp.05, 2015,
  7. Common Genetic Variations in the MUC5AC Gene are Not Related to Helicobacter pylori Serologic Status vol.15, pp.24, 2015,
  8. Helicobacter pylori Infection Impacts on Functional Dyspepsia in Thailand vol.15, pp.24, 2015,
  9. infection, as potential biomarkers for the early diagnosis of gastric cancer vol.22, pp.1, 2016,