@article{b8c3b4125a2a4ba29d9ae057238dd52f,
title = "A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population",
abstract = "Through a genome-wide association analysis with a total of 7,035 individuals with duodenal ulcer and 25,323 controls from Japan, we identified two susceptibility loci at the PSCA gene (encoding prostate stem cell antigen) at 8q24 and at the ABO blood group locus at 9q34. The C allele of rs2294008 at PSCA was associated with increased risk of duodenal ulcer (odds ratio (OR) = 1.84; P = 3.92 x 10 -33) in a recessive model but was associated with decreased risk of gastric cancer (OR = 0.79; P = 6.79 x 10 -12), as reported previously. The T allele of rs2294008 encodes a translation initiation codon upstream of the reported site and changes protein localization from the cytoplasm to the cell surface. rs505922 at ABO was also associated with duodenal ulcer in a recessive model (OR = 1.32; P = 1.15 x 10 -10). Our findings demonstrate a role for genetic variants in the pathogenesis of duodenal ulcer.",
author = "Chizu Tanikawa and Yuji Urabe and Keitaro Matsuo and Michiaki Kubo and Atsushi Takahashi and Hidemi Ito and Kazuo Tajima and Naoyuki Kamatani and Yusuke Nakamura and Koichi Matsuda",
note = "Funding Information: Sample collection. We obtained DNA from 7,035 subjects with duodenal ulcer from the BioBank Japan Personalized Medicine Project of the Ministry of Education, Culture, Sports, Science and Technology of Japan35. In the BioBank Japan Project, DNA and serum of subjects were collected through a collaborating network of 66 hospitals throughout Japan (see Supplementary Note). Clinical information on subjects, including drug history, was obtained from clinical records of each participating hospital. More than 200,000 individuals with 47 diseases, irrespective of prior treatment, were enrolled in this project from 2003 through 2009. A list of participating hospitals is provided at the BioBank Japan website (see URLs). A total of 25,323 control samples without duodenal ulcer were obtained from BioBank Japan or from healthy volunteers from the Midosuji Rotary Club in Osaka, Japan. Controls for the GWAS included subjects with colon, breast, prostate, lung, pancreatic or liver cancer, diabetes, myocardial infarction, brain infarction, arteriosclerosis obliterans, atrial fibrillation, cholangiocarcinoma, drug eruption, liver cirrhosis and amyotrophic lateral sclerosis. Controls for the replication analysis included healthy volunteers and individuals with chronic hepatitis B or C, cervical, esophageal, hematological or ovarian cancer, pulmonary tuberculosis, keroidosis and endometriosis. Controls for gastric cancer included subjects with diabetes, myocardial infarction, brain infarction, arteriosclerosis obliterans, atrial fibrillation, drug eruption, liver cirrhosis and amyotrophic lateral sclerosis. A total of 37 individuals with H. pylori–positive duodenal ulcer or 793 healthy controls were randomly selected from noncancer outpatient visitors to the Aichi Cancer Center Hospital in Nagoya, Japan between January 2001 and November 2005 (ref. 36). H. pylori infection status was confirmed by determining plasma levels of IgG to the bacterium with a commercially available direct ELISA kit (Eiken Kagaku). Positivity for H. pylori infection was defined by H. pylori–specific IgG levels of greater than 10 U/ml in serum. We excluded subjects with gastric cancer or gastric ulcer from all controls. We excluded individuals treated with nonsteroidal antiinflammatory drugs or steroid hormones from both duodenal ulcer cases and controls. We excluded subjects with a history of any cancer or peptic ulcer from the controls for gastric cancer. All subjects were Japanese and provided written informed consent. The clinical and demographic details of the samples are summarized in Table 1. This research project was approved by the ethical committees of The University of Tokyo, RIKEN and the Aichi Cancer Center.",
year = "2012",
month = apr,
doi = "10.1038/ng.1109",
language = "English",
volume = "44",
pages = "430--434",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "4",
}
