title: Helicobacter pylori virulence genes in the five largest islands of Indonesia.
abstract: BACKGROUND
  It remains unclear whether the low incidence of gastric cancer in Indonesia is due to low infection rates only or is also related to low Helicobacter pylori pathogenicity. We collected H. pylori strains from the five largest islands in Indonesia and evaluated genetic virulence factors.
  
  
  METHODS
  The genotypes of H. pylori virulence factors were determined by polymerase chain reaction (PCR)-based sequencing. Histological severity of the gastric mucosa was classified into 4 grades, according to the updated Sydney system.
  
  
  RESULTS
  A total of 44 strains were analyzed. Forty-three (97.7 %) were cagA-positive: 26 (60.5 %) were East-Asian-type-cagA, 9 (20.9 %) were Western-type-cagA, and 8 (18.6 %) were novel ABB-type, most of which were obtained from Papuan. EPIYT sequences were more prevalent than EPIYA sequences (P = 0.01) in the EPIYA-B motif of all types of cagA. The majority of cagA-positive strains (48.8 %, 21/43) had a 6-bp deletion in the first pre-EPIYA region. Subjects infected with East-Asian-type-cagA strains with a 6-bp deletion had significantly lower inflammation and atrophy scores in the corpus than those infected with Western-type-cagA strains (both P = 0.02). In total, 70.4 % of strains possessed the vacA s1m1 genotype and 29.5 % were m2. All strains from peptic ulcer patients were of the iceA1 genotype, which occurred at a significantly higher proportion in peptic ulcer patients than that in gastritis patients (55.3 %, P = 0.04). The double positive genotype of jhp0562/β-(1,3)galT was predominant (28/44, 63.6 %), and subjects infected with this type had significantly higher inflammation scores in the corpus than those with the jhp0562 negative/β-(1,3)galT positive genotype (mean [median]; 1.43 [1] vs. 0.83 [1], P = 0.04). There were significant differences in cagA and pre-EPIYA cagA type, oipA status, and jhp0562/β-(1,3)galT type among different ethnic groups (P < 0.05).
  
  
  CONCLUSIONS
  In addition to a low H. pylori infection rate, the low incidence of gastric cancer in Indonesia might be attributed to less virulent genotypes in predominant strains, which are characterized by the East-Asian-type-cagA with a 6-bp deletion and EPIYT motif, a high proportion of m2, dupA negative or short type dupA, and the jhp0562/β-(1,3)galT double positive genotype.
authors.affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593 Japan ; Gastroentero-Hepatology Division, Department of Internal Medicine, Airlangga University Faculty of Medicine, Surabaya, 60131 Indonesia ; Institute of Tropical Disease, Airlangga University, Surabaya, 60115 Indonesia.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Miftahussurur
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, 10430 Indonesia.
authors.forename: Ari Fahrial
authors.initials: AF
authors.lastname: Syam
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, 10430 Indonesia.
authors.forename: Dadang
authors.initials: D
authors.lastname: Makmun
authors.affiliation: Gastroentero-Hepatology Division, Department of Internal Medicine, Airlangga University Faculty of Medicine, Surabaya, 60131 Indonesia.
authors.forename: Iswan Abbas
authors.initials: IA
authors.lastname: Nusi
authors.affiliation: Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan, 20136 Indonesia.
authors.forename: Lukman Hakim
authors.initials: LH
authors.lastname: Zein
authors.affiliation: Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan, 20136 Indonesia.
authors.lastname: Zulkhairi
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Center of Gastroentero-Hepatology, Hasanuddin University, Makassar, 90245 Indonesia.
authors.forename: Fardah
authors.initials: F
authors.lastname: Akil
authors.affiliation: Department of Internal Medicine, Santo Antonius Hospital, Pontianak, 78115 Indonesia.
authors.forename: Willi Brodus
authors.initials: WB
authors.lastname: Uswan
authors.affiliation: Department of Internal Medicine, Yowari Hospital, Jayapura, 99352 Indonesia.
authors.forename: David
authors.initials: D
authors.lastname: Simanjuntak
authors.affiliation: Department of Molecular Pathology, Oita University Faculty of Medicine, Yufu, 879-5593 Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Institute of Tropical Disease, Airlangga University, Surabaya, 60115 Indonesia.
authors.forename: Pangestu
authors.initials: P
authors.lastname: Adi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, 10430 Indonesia.
authors.forename: Amanda Pitarini
authors.initials: AP
authors.lastname: Utari
authors.affiliation: Institute of Tropical Disease, Airlangga University, Surabaya, 60115 Indonesia.
authors.forename: Yudith Annisa Ayu
authors.initials: YA
authors.lastname: Rezkitha
authors.affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593 Japan.
authors.forename: Phawinee
authors.initials: P
authors.lastname: Subsomwong
authors.affiliation: Institute of Tropical Disease, Airlangga University, Surabaya, 60115 Indonesia.
authors.lastname: Nasronudin
authors.affiliation: Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593 Japan ; Department of Gastroenterology and Hepatology, Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Houston, TX 77030 USA.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamaoka
keywords: Helicobacter pylori; Indonesia; Virulence factors