Evaluation of the risk of infectious/immunity-related diseases conferred by genetic polymorphisms in the HLA system

• Project/Area Number: 26293076
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: 地方独立行政法人佐賀県医療センター好生館(ライフサイエンス研究所) (2016-2017); Nagasaki University (2014-2015)
• Principal Investigator: YASUNAMI Michio 地方独立行政法人佐賀県医療センター好生館(ライフサイエンス研究所), ライフサイエンス研究所, 部長 (80244127)
• Co-Investigator(Kenkyū-buntansha): 右田 清志 福島県立医科大学, 医学部, 教授 (60264214)
• Co-Investigator(Renkei-kenkyūsha): ARIYOSHI Koya 長崎大学, 熱帯医学研究所, 教授 (30311400) ; HIRAI Hirohisa 京都大学, 霊長類研究所, 教授 (10128308) ; KAWAI Satoru 獨協医科大学, 医学部, 准教授 (70275733)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
• Keywords: ゲノム / 疾患リスク / 表現型分析 / 感染症 / 免疫異常 / 疾患発症・重症化リスク / ケース・コントロール研究

Outline of Final Research Achievements

HLA is composed of highly polymorphic molecules mainly due to variations in the regions involved in specificity determination during antigen presentation processes. Thus the HLA polymorphism leads to heterogeniety in immune response between individuals. In this study, we revealed an inhibitory effect of certain HLA class II alleles in several different infectious/immunity-related diseases. These results suggested the presence of additional underlying common regulatory mechanism(s) in immunity/inflammation via HLA class II molecules.

Research Products

• [Int'l Joint Research] 国立医科学研究所(タイ)
• [Int'l Joint Research] ニャチャン・パスツール研究所/国立衛生疫学研究所(ベトナム)
• [Int'l Joint Research] 国立衛生疫学研究所/ホーチミン市パスツール研究所(ベトナム)
• [Int'l Joint Research] タイ保健省医科学局/国立ランパン病院デイケアセンター(タイ)
• [Int'l Joint Research] 保健省医学研究所(タイ)
• [Int'l Joint Research] ホーチミン市パスツール研究所(ベトナム)
• [Journal Article] The Impact of Hla Allele-Kir Pairs on Disease Outcome in Hiv-Infected Thai Population (2018)
  • Author(s): Mori Masahiko、Wichukchinda Nuanjun、Miyahara Reiko、Rojanawiwat Archawin、Pathipvanich Panita、Miura Toshiyuki、Yasunami Michio、Ariyoshi Koya、Sawanpanyalert Pathom
  • Journal Title: JAIDS Journal of Acquired Immune Deficiency Syndromes Volume: 78 Issue: 3 Pages: 1-1
  • DOI: 10.1097/qai.0000000000001676
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Accuracy of High-Throughput Nanofluidic PCR-Based Pneumococcal Serotyping and Quantification Assays Using Sputum Samples for Diagnosing Vaccine Serotype Pneumococcal Pneumonia: Analyses by Composite Diagnostic Standards and Bayesian Latent Class Models (2018)
  • Author(s): Kakiuchi Satoshi、Suzuki Motoi、Dhoubhadel Bhim Gopal、Furumoto Akitsugu、Ito Hiroyuki、Matsuki Kei、Tsuchihashi Yoshiko、Asoh Norichika、Yasunami Michio、Ariyoshi Koya、Morimoto Konosuke
  • Journal Title: Journal of Clinical Microbiology Volume: 56 Issue: 5
  • DOI: 10.1128/jcm.01874-17
  • NAID: 120006987336
  • Peer Reviewed
• [Journal Article] HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype (2017)
  • Author(s): Oka Shomi、Furukawa Hiroshi、Yasunami Michio、他
  • Journal Title: PLOS ONE Volume: 12 Issue: 10 Pages: e0187325-e0187325
  • DOI: 10.1371/journal.pone.0187325
  • NAID: 120007128808
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of HLA-DRB1 alleles on susceptibility and clinical manifestations in Japanese patients with adult onset Still's disease. (2017)
  • Author(s): Asano T, Furukawa H, Sato S, Yashiro M, Kobayashi H, Watanabe H, Suzuki E, Ito T, Ubara Y, Kobayashi D, Iwanaga N, Izumi Y, Fujikawa K, Yamasaki S, Nakamura T, Koga T, Shimizu T, Umeda M, Nonaka F, Yasunami M, Ueki Y, Eguchi K, Tsuchiya N, Tohma S, Yoshiura KI, Ohira H, Kawakami A, Migita K.
  • Journal Title: Arthritis Res Ther. Volume: 19 Issue: 1 Pages: 199-199
  • DOI: 10.1186/s13075-017-1406-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Principal contribution of HLA-DQ alleles, DQB1*06:04 and DQB1*03:01, to disease resistance against primary biliary cholangitis in a Japanese population (2017)
  • Author(s): Yasunami Michio、Nakamura Hitomi、Tokunaga Katsushi、Kawashima Minae、Nishida Nao、Hitomi Yuki、Nakamura Minoru
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 11093-11093
  • DOI: 10.1038/s41598-017-11148-6
  • Peer Reviewed / Open Access
• [Journal Article] Risk for Death among Children with Pneumonia, Afghanistan (2017)
  • Author(s): Zabihullah Rahmani、Dhoubhadel Bhim G.、Rauf Ferogh A.、Shafiq Sahab A.、Suzuki Motoi、Watanabe Kiwao、Yoshida Lay M.、Yasunami Michio、Zabihullah Salihi、Parry Christopher M.、Mirwais Rabi、Ariyoshi Koya
  • Journal Title: Emerging Infectious Diseases Volume: 23 Issue: 8 Pages: 1404-1408
  • DOI: 10.3201/eid2308.151550
  • NAID: 120006987439
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of the functional variant driving ORMDL3 and GSDMB expression in human chromosome 17q12-21 in primary biliary cholangitis (2017)
  • Author(s): Hitomi Yuki、Kojima Kaname、Kawashima Minae、Kawai Yosuke、Nishida Nao、Aiba Yoshihiro、Yasunami Michio、Nagasaki Masao、Nakamura Minoru、Tokunaga Katsushi
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 2904-2904
  • DOI: 10.1038/s41598-017-03067-3
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population. (2017)
  • Author(s): Kawashima M, Honda M, Nakamura M. et al.
  • Journal Title: Hum Mol Genet. Volume: - Pages: 650-659
  • DOI: 10.1093/hmg/ddw406
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A significant association between rs8067378 at 17q12 and invasive cervical cancer originally identified by a genome-wide association study in Han Chinese is replicated in a Japanese population. (2016)
  • Author(s): Miura K, Mishima H, Yasunami M, Kaneuchi M, Kitajima M, Abe S, Higashijima A, Fuchi N, Miura S, Yoshiura KI, Masuzaki H.
  • Journal Title: J Hum Genet. Volume: 61(9) Issue: 9 Pages: 793-796
  • DOI: 10.1038/jhg.2016.50
  • NAID: 40020938176
  • Peer Reviewed
• [Journal Article] Familial Mediterranean fever is no longer a rare disease in Japan. (2016)
  • Author(s): Migita K, Izumi Y, Jiuchi Y, Iwanaga N, Kawahara C, Agematsu K, Yachie A, Masumoto J, Fujikawa K, Yamasaki S, Nakamura T, Ubara Y, Koga T, Nakashima Y, Shimizu T, Umeda M, Nonaka F, Yasunami M, Eguchi K, Yoshiura K, Kawakami A.
  • Journal Title: Arthritis Res Ther. Volume: 18 Issue: 1 Pages: 175-175
  • DOI: 10.1186/s13075-016-1071-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population. (2016)
  • Author(s): Maeda Y, Migita K, Higuchi O, Mukaino A, Furukawa H, Komori A, Nakamura M, Hashimoto S, Nagaoka S, Abiru S, Yatsuhashi H, Matsuo H, Kawakami A, Yasunami M, Nakane S
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0146048-e0146048
  • DOI: 10.1371/journal.pone.0146048
  • NAID: 120007129614
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines. (2015)
  • Author(s): Vasquez Velasquez C, Roman AD, Lan NT, Huy NT, Mercado ES, Espino FE, Perez ML, Huong VT, Thuy TT, Tham VD, Nga CT, Ha TT, Bilar JM, Bajaro JD, Baello BQ, Kikuchi M, Yasunami M, Morita K, Watanabe N, Karbwang J, Hirayama K.
  • Journal Title: Hum Immunol. Volume: 76 Issue: 5 Pages: 318-323
  • DOI: 10.1016/j.humimm.2015.03.009
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever. (2015)
  • Author(s): Yasunami M, Nakamura H, Nakamura A, Yazaki M, Kishida D et al.
  • Journal Title: PLoS One Volume: May 14;10(5) Issue: 5 Pages: e0125938-e0125938
  • DOI: 10.1371/journal.pone.0125938
  • NAID: 120007100158
  • Peer Reviewed / Open Access
• [Journal Article] The effect of KIR2D-HLA-C receptor-ligand interactions on clinical outcome in a HIV-1 CRF01_AE-infected Thai population. (2015)
  • Author(s): Masahiko Mori, Nuanjun Wichukchinda, Reiko Miyahara, Archawin Rojanawiwat, Panita Pathipvanich, Naho Tsuchiya, Toshiyuki Miura, Michio Yasunami, Koya Ariyoshi, and Pathom Sawanpanyalert
  • Journal Title: AIDS Volume: 29 Issue: 13 Pages: 1607-1615
  • DOI: 10.1097/qad.0000000000000747
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of disease-promoting HLA class I and protective class II modifiers in Japanese patients with familial Mediterranean fever (2015)
  • Author(s): Yasunami M, Nakamura H, Agematsu K, Nakamura A, Yazaki M, Kishida D, Yachie A, Toma T, Masumoto J, Ida H, Koga T, Kawakami A, Eguchi K, Furukawa H, Nakamura T, Nakamura M, Migita K
  • Journal Title: PLoS One Volume: 印刷中
  • NAID: 120007100158
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines (2015)
  • Author(s): Vasquez Velasquez C, Roman AD, Lan NT, Huy NT, Mercado ES, Espino FE, Perez ML, Huong VT, Thuy TT, Tham VD, Nga CT, Ha TT, Bilar JM, Bajaro JD, Baello BQ, Kikuchi M, Yasunami M, Morita K, Watanabe N, Karbwang J, Hirayama K
  • Journal Title: Hum Immunol Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Increased prevalence of MEFV exon 10 variants in Japanese patients with adult onset Still's disease (2015)
  • Author(s): Nonaka F, Migita K, Jiuchi Y, Shimizu T, Umeda M, Iwamoto N, Fujikawa K, Izumi Y, Mizokami A, Nakashima M, Ueki Y, Yasunami M, Kawakami A, Eguchi K
  • Journal Title: Clin Exp Immunol Volume: 179 Issue: 3 Pages: 392-397
  • DOI: 10.1111/cei.12463
  • Peer Reviewed
• [Journal Article] Dysregulated mature IL-1β production in familial Mediterranean fever. (2015)
  • Author(s): Migita K, Izumi Y, Fujikawa K, Agematsu K, Masumoto J, Jiuchi Y, Kozuru H, Nonaka F, Shimizu T, Nakamura T, Iwanaga N, Furukawa H, Yasunami M, Kawakami A, Eguchi K.
  • Journal Title: Rheumatology (Oxford) Volume: 54 Issue: 4 Pages: 660-665
  • DOI: 10.1093/rheumatology/keu359
  • Peer Reviewed
• [Journal Article] IL-18 serum concentration is markedly elevated in typical familial Mediterranean fever with M694I mutation and can distinguish it from atypical type (2014)
  • Author(s): Yamazaki T, Shigemura T, Kobayashi N, Honda K, Yazaki M, Masumoto J, Migita K, Agematsu K
  • Journal Title: Mod Rheumatol Volume: 22 Pages: 1-3
  • Peer Reviewed
• [Journal Article] Population Based Cohort Study for Pediatric Infectious Diseases Research in Vietnam (2014)
  • Author(s): Yoshida LM, Suzuki M, Thiem VD, Smith WP, Tsuzuki A, Huong VT, Takahashi K, Miyakawa M, Anh NT, Watanabe K, Ai NT, Tho le H, Kilgore P, Yoshino H, Toizumi M, Yasunami M, Moriuchi H, Anh DD, Ariyoshi K
  • Journal Title: Tropical Medicine and Health Volume: 42 Issue: 2SUPPLEMENT Pages: S47-S58
  • DOI: 10.2149/tmh.2014-S07
  • NAID: 130004463458
  • ISSN: 1348-8945, 1349-4147
  • Peer Reviewed
• [Journal Article] MEFV gene polymorphisms and TNFRSF1A mutation in patients with inflammatory myopathy with abundant macrophages (2014)
  • Author(s): Fujikawa K, Migita K, Shigemitsu Y, Umeda M, Nonaka F, Tamai M, Nakamura H, Mizokami A, Tsukada T, Origuchi T, Yonemitsu N, Yasunami M, Kawakami A, Eguchi K
  • Journal Title: Clin Exp Immunol Volume: 178 Issue: 2 Pages: 224-228
  • DOI: 10.1111/cei.12407
  • Peer Reviewed
• [Journal Article] Serum amyloid A induces NLRP-3-mediated IL-1β secretion in neutrophils. (2014)
  • Author(s): Migita K, Izumi Y, Jiuchi Y, Kozuru H, Kawahara C, Nakamura M, Nakamura T, Agematsu K, Masumoto J, Yasunami M, Kawakami A, Eguchi K.
  • Journal Title: PLoS One Volume: 9 Issue: 5 Pages: e96703-e96703
  • DOI: 10.1371/journal.pone.0096703
  • Peer Reviewed / Open Access
• [Journal Article] HLA-B*35:05 is a protective allele with a unique structure among HIV-1 CRF01_AE-infected Thais, in whom the B*57 frequency is low. (2014)
  • Author(s): Mori M, Wichukchinda N, Miyahara R, Rojanawiwat A, Pathipvanich P, Maekawa T, Miura T, Goulder P, Yasunami M, Ariyoshi K, Sawanpanyalert P.
  • Journal Title: AIDS Volume: 28 Issue: 7 Pages: 959-967
  • DOI: 10.1097/qad.0000000000000206
  • Peer Reviewed
• [Presentation] Environment-dependent effect of ALDH2*2 on childhood respiratory infections was found in a birth cohort study in Vietnam (ALDH2バリアントアレルは環境要因に依存して乳幼児期呼吸器感染症リスクに寄与している) (2017)
  • Author(s): 安波道郎、宮原麗子、吉田レイミント、中村仁美、高橋健介、Vu Dinh Thiem、Dang Duc Anh、Le Huu Tho、森内浩幸、有吉紅也
  • Organizer: 日本人類遺伝学会 第62回大会
• [Presentation] Principal contribution of HLA-DQ alleles, DQB1*06:04 and DQB1*03:01, to disease resistance against primary biliary cholangitis in Japanese population (2017)
  • Author(s): Michio Yasunami, Hitomi Nakamura, Katsushi Tokunaga, Minae Kawashima, Nao Nishida, Yuki Hitomi, Minoru Nakamura
  • Organizer: 日本免疫学会 第46回総会・学術集会
• [Presentation] A profound effect of common HLA polymorphisms on the survival of the patients with HIV infection in the pre-antiviral era in Thailand. (2016)
  • Author(s): Michio Yasunami, Nuanjun Wichukchinda, Reiko Miyahara, Naho Tsuchiya, Hitomi Nakamura, Masahiko Mori, Archawin Rojanawiwat, Panita Pathipvanic, Pathom Sawanpanyalert, Koya Ariyoshi
  • Organizer: ASHG Annual Meeting 2016
  • Place of Presentation: バンクーバー（カナダ）
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] Effect of HLA polymorphisms on the survival in the patient with AIDS. (2016)
  • Author(s): Michio Yasunami, Nuanjun Wichukchinda, Reiko Miyahara, Naho Tsuchiya, Hitomi Nakamura, Masahiko Mori, Archawin Rojanawiwat, Panita Pathipvanic, Pathom Sawanpanyalert, Koya Ariyoshi
  • Organizer: ICHG2016 [The 13th International Congress of Human Genetics]
  • Place of Presentation: 京都
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Dissection of HLA class II in Japanese primary biliary cirrhosis: epistasis of protective HLA-DQ allele and additional contribution of HLA-DP allele. (2015)
  • Author(s): M Yasunami, H Nakamura, K Tokunaga, M Kawashima, N Nishida, Y Hitomi, M Nakamura.
  • Organizer: The 65th Annual Meeting of the American Society of Human Genetics.
  • Place of Presentation: Baltimore, USA.
  • Year and Date: 2015-10-06
  • Int'l Joint Research
• [Presentation] HLA confer the risk of familial Mediterranean fever in Japanese population (2014)
  • Author(s): Michio Yasunami
  • Organizer: The 64th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] New association of HLA class II and non-responsiveness to hepatitis B vaccine was identified by a birth-cohort study in Vietnam (2014)
  • Author(s): Michio Yasunami
  • Organizer: The 13th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji Yumebutai International Conference Center, Nara, Japan
  • Year and Date: 2014-09-23 – 2014-09-26
• [Presentation] 日本人原発性胆汁性肝硬変の発症、進行におけるHLA多型の効果 (2014)
  • Author(s): 安波道郎
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: ホテルニューオオタニ、東京(千代田区)
  • Year and Date: 2014-05-29 – 2014-05-30