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inequalityGoal 11: Sustainable cities and communitiesGoal 12: Responsible consumption and productionGoal 13: Climate actionGoal 14: Life below waterGoal 15: Life on landGoal 16: Peace, justice and strong institutionsGoal 17: Partnership for the goalsAreasSocial sciencesMathematics and physicsChemistryEngineering sciencesInformaticsBiological sciencesAgriculture and EnvironmentMedicine, dentistry and pharmacologyHumanitiesEventsEventsEvent categoriesTalksOpen lecturesUniversity activitiesEvent areasSocial sciencesEvent locationsRokkodai 1st CampusOff-campusOnlineEvent audiencesStudentsAudienceProspective studentsCurrent studentsAlumsCorporate and societyFaculty and staff CloseNews TopCategoriesPress releasesRead in日本語2018.07.26Susceptible genes identified for childhood chronic kidney disease Medicine, dentistry and pharmacologyEmbryonic medicine / PediatricsNephrologyNephrotic syndromeGenome analysisIntractable diseasesChildhood nephrotic syndrome is the most frequently occurring chronic kidney disease among children. A Japanese research team has identified a group of genes that are strongly related to the development of childhood nephrotic syndrome. The results of this study could shed light on the underlying mechanism for this disease. These findings were published on July 16 in the online edition of Journal of the American Society of Nephrology.Also known as nephrosis, childhood nephrotic syndrome is an incurable disease with an unknown cause, characterized by large amounts of protein leaving the body in the patient’s urine, and protein levels in the bloodstream becoming extremely low. The majority of patients develop steroid-sensitive nephrotic syndrome that responds to steroids and immune-suppressing drugs, and go into remission, but at least 20% of cases are resistant strains that recur repeatedly during adulthood. It is thought that people who are genetically predisposed develop the syndrome when exposed to an immunological stimulus such as infection. This study aimed to identify the genes that make Japanese infants susceptible to steroid-sensitive nephrotic syndrome.Figure 1: Hypothesis for the onset mechanism of childhood steroid-sensitive nephrotic syndromeFigure 2: Results of the GWAS (Manhattan plot)The team identified a significant (P< 5x10-8) genome-wide signal in the short arm of human chromosome 6Researchers collected genetic DNA from 1,300 sufferers of childhood nephrotic syndrome in Japan. The study targeted 224 of the samples with childhood steroid-sensitive nephrotic syndrome and a control group of 419 healthy Japanese people, to perform a genome-wide association study (GWAS) using the Affymetrix Japonica Array. This enabled them to identify SNPs with a significant genome-wide association in the HLA-DR/DQ area of the short arm of human chromosome 6. They then identified the HLA haplotypes (gene groups) with the lowest and highest risks of developing the syndrome. They confirmed this result with a different cohort of 213 samples of infant steroid-sensitive nephrotic syndrome and a control group of 710 healthy Japanese individuals.The HLA haplotype showing the highest risk of development is HLA-DRB1*08:02-HLA-DQB1*03:02 (odds ratio: 3.60) and the HLA haplotype showing the lowest risk of development is HLA-DRB1*13:02-HLA-DQB1*06:04 (odds ratio: 0.10). This is the first time these haplotypes have been identified to such a high degree of precision.Figure 3: enlargement of the HLA-DR/DQ areaThe genome wide significant area in Figure 2 was the HLA-DR/DQ areaThis research was carried out by a team led by Professor Kazumoto Iijima, Associate Professor Kandai Nozu and Ms. Tomoko Horinouchi (Kobe University Graduate School of Medicine); in collaboration with Professor Katsushi Nokunaga, Assistant Professor Yuki Hitomi and Xiaoyuan Jia (Tokyo University Graduate School of Medicine); and Professor Masao Nagasaki and Assistant Professor Yosuke Kawai (Tohoku Medical Megabank Organization).The research team is currently carrying out a genome-wide association study using the Japonica Array that targets 1,152 samples from infant nephrotic syndrome sufferers and a control group of 2,807 healthy Japanese individuals.“With this study there is a high possibility that we will be able to identify other susceptible genes,” comments Professor Iijima. “In the future we would like to engage in international collaboration to confirm whether the susceptible genes are the same for people worldwide.”This research is part of an order-made program by the Japan Agency for Medical Research and Development (AMED) supported by the Research Consortium on Genetics of Childhood Ideopathic Nephrotic Syndrome in Japan with the cooperation of infant kidney specialist physicians throughout Japan.Journal informationTitle“Strong Association of HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population”DOI10.1681/ASN.2017-08-0859AuthorsXiaoyuan Jia, Tomoko Horinouchi, Yuki Hitomi, Akemi Shono, Seik-Soon Khor, Yosuke Omae, Kaname Kojima, Yosuke Kawai, Masao Nagasaki, Yoshitsugu Kaku, Takayuki Okamoto, Yoko Ohwada, Kazuhide Ohta, Yusuke Okuda, Rika Fujimaru, Ken Hatae, Naonori Kumagai, Emi Sawanobori, Hitoshi Nakazato, Yasufumi Ohtsuka, Koichi Nakanishi, Yuko Shima, Ryojiro Tanaka, Akira Ashida, Koichi Kamei, Kenji Ishikura, Kandai Nozu, Katsushi Tokunaga, Kazumoto Iijima, for the Research Consortium on Genetics of Childhood Idiopathic Nephrotic Syndrome in JapanJournalJournal of the American Society of NephrologyResearchersIijima KazutmoProfessorGraduate School of MedicineNodu KandaiProfessorGraduate School of MedicineHorinouchi TomokoLecturerHospitalSHONO AkemiGraduate School of MedicineSDGs)">Graduate School of MedicineSHAREMore from these researchersPress releases2021.12.02Medicine, dentistry and pharmacologyImpact of COVID-related state of emergency declarations on asthma exacerbations in childrenPress releases2021.09.01Medicine, dentistry and pharmacologyStudy reveals possibility that many Japanese have undiagnosed Gitelman SyndromePress releases2020.08.07Medicine, dentistry and pharmacologyAlport Syndrome: Research highlights link between genotype and treatment effectivenessPress releases2020.07.03Medicine, dentistry and pharmacologyDiscovery of new disease-susceptibility gene for steroid-sensitive nephrotic syndromeMore about these topicsPress releases2020.06.25Medicine, dentistry and pharmacologyNew treatment method for Alport Syndrome uses antisense oligonucleotidesPress releases2017.05.17Medicine, dentistry and pharmacologyControl mechanism unveiled for gene that causes Opitz syndromePress releases2023.08.25Medicine, dentistry and pharmacologyNovel autoantibodies are implicated in hypertensive disorders of pregnancy, fetal growth restriction, and other pregnancy disordersPress releases2022.05.02Medicine, dentistry and pharmacologyDoes autism begin in the womb?ページの先頭へ1-1, Rokkodai-cho, Nada-ku, Kobe, 657-8501, JAPANProspective studentsCurrent studentsAlumsCorporate and societyFaculty and staffContactAccessJobsOfficial social media accountsCampus calendarPrivacy policySite policySite map© Kobe University