2000 Fiscal Year Annual Research Report

日本人2型糖尿病原因遺伝子の全ゲノムレベル解析

Research Project

Project/Area Number	12204102
Research Institution	Tokyo Women's Medical University
Principal Investigator	岩崎直子東京女子医科大学, 医学部, 講師 (70203370)
Co-Investigator(Kenkyū-buntansha)	岩本安彦東京女子医科大学, 医学部, 教授 (60143434)
Keywords	多因子遺伝 / 2型糖尿病 / 遺伝子 / 罹患同胞対法 / ミトコンドリア遺伝子 / 腎障害 / HNF / MODY
Research Abstract	糖尿病の遺伝素因を明らかにするために,単一遺伝疾患であるMODYについては候補遺伝子のmutation screeningを,また,多因子遺伝疾患である2型糖尿病に関しては,罹患同胞対法を用いて全ゲノムスクリーニングを継続している.MODYに関しては,peroxisome proloferator-activated receptor α(PPARα),neurogenic differentiation 4(NEUROD4),hepatocyte nuclear factor(HNF)3β,HNF4γ,neurogenin 3(NEUROG3)の各遺伝子のスクリーニングを施行した.これらの5種類の遺伝子の中には明らかな病因と考えられる変異は認めなかったため,日本人においては上記の遺伝子が糖尿病の素因として大きく関与しているとは考え難いと言える.新たなHNF-1β遺伝子変異を見い出した.合併症の遺伝素因として,末期腎不全に至る糖尿病患者ではミトコンドリア遺伝子3243変異陽性者が有意に高いことを認めた. 罹患同胞対法を用いた日本人2型糖尿病疾患感受性遺伝子座位に関しては,解析を終了し第9番染色体上に統計学的に有意の座位を認めた.現在は,関心領域のnarrowingのために,さらに近傍のマーカーのtypingを行っている.また,メキシコ系アメリカ人で報告されたNIDDM1(Calpain10)は日本人では糖尿病発症との関連は少なさそうである.

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Manami Hara: "Identfication of three missense mutations in peroxisome proliferator-activated receptor a in Japanese subjects with MODY but no association with diabetes"J Hum Genet 46:2001. 46(in press). (2001)
[Publications] N.Iwasaki,: "Prevalence of the A-to-G mutation at nucleotide 3243 of the mitochondrial tRNALeu(UUR)gene in Japanese patients with diabetes mellitus and end-stage renal disease"J Hum Genet 46:2001. 46(in press). (2001)
[Publications] Naoko Iwasaki: "Mutations in the hepatocyte nuclear factor-1b(MODY5)gene are not a major factor contributing to end-stage renal disease in Japanese people with diabetes mellitus"Diabetologia 44:2001. 44(in press). (2001)
[Publications] Naoko Iwasaki: "A Novel Splice Site Mutation in the Hepatocyte Nuclear Factor-1βGene, IVS2nt+1G>A, Associated with Maturity-Onset Diabetes of the Young, Agenesis of the Left Kidney and Bicornuate Uterus"Diabctologia 44:127-128,2001. 44. 127-128 (2001)
[Publications] Yohko Horikawa: "β-Cell Transcription Factors and Diabetes : No Evidence for Diabetes Associated Mutations in the Gene Encoding the Basic-Helix-Loop-Helix Transcription Factor Neurogenic Differentiation 4(NEUROD4)in Japanese Patients with MODY"Diabetes 49:1955-1957,2000. 49. 1955-1957 (2000)
[Publications] Yukio Horikawa: "Genetic variation in the calpain 10 gene(CAPN10)is associated with type 2 diabetes mellitus"Nature Genet.26:163-175,2000. 26. 163-175 (2000)
[Publications] Yoshinori Hinokio: "β-Cell Transcription Factors and Diabetes : No Evidence for Diabetes Associated Mutations in the Hepatocyte Nuclear Factor-3b Gene (HNF3B) in Japanese patients with MODY"Diabetes. 49. 302-305 (2000)
[Publications] Manami Hara: "No diabetes-associated mutations in the coding region of the hepatocyte nuclear factor-4γ (HNF4G) in Japanese patients with MODY"Diabetologia. 43. 1064-1069 (2000)
[Publications] 岩崎直子,岡芳知編: "糖尿病学2001 2型糖尿病遺伝子カルパイン10-ゲノムワイドスクリーニングの成果と今後の展望"診断と治療社(未確認). (2001)
[Publications] 岩崎直子,春日雅人編: ""糖尿病"UPDATE糖尿病遺伝子の現況メビオ別冊「Multiple Risk Factor Syndrome」4 Multiple Risk Factorと高血圧"メジカルビュー社. 179 (2000)
[Publications] 岩崎直子,門脇孝編: "医学のあゆみ第5土曜特集糖尿病の分子医学 ■糖尿病の分子メカニズム2型糖尿病疾患感受性遺伝子"医歯薬出版. 635 (2000)

2000 Fiscal Year Annual Research Report

日本人2型糖尿病原因遺伝子の全ゲノムレベル解析

Principal Investigator

岩崎 直子 東京女子医科大学, 医学部, 講師 (70203370)

Research Products

[Publications] Manami Hara: "Identfication of three missense mutations in peroxisome proliferator-activated receptor a in Japanese subjects with MODY but no association with diabetes"J Hum Genet 46:2001. 46(in press). (2001)

[Publications] N.Iwasaki,: "Prevalence of the A-to-G mutation at nucleotide 3243 of the mitochondrial tRNALeu(UUR)gene in Japanese patients with diabetes mellitus and end-stage renal disease"J Hum Genet 46:2001. 46(in press). (2001)

[Publications] Naoko Iwasaki: "Mutations in the hepatocyte nuclear factor-1b(MODY5)gene are not a major factor contributing to end-stage renal disease in Japanese people with diabetes mellitus"Diabetologia 44:2001. 44(in press). (2001)

[Publications] Naoko Iwasaki: "A Novel Splice Site Mutation in the Hepatocyte Nuclear Factor-1βGene, IVS2nt+1G>A, Associated with Maturity-Onset Diabetes of the Young, Agenesis of the Left Kidney and Bicornuate Uterus"Diabctologia 44:127-128,2001. 44. 127-128 (2001)

[Publications] Yukio Horikawa: "Genetic variation in the calpain 10 gene(CAPN10)is associated with type 2 diabetes mellitus"Nature Genet.26:163-175,2000. 26. 163-175 (2000)

[Publications] Yoshinori Hinokio: "β-Cell Transcription Factors and Diabetes : No Evidence for Diabetes Associated Mutations in the Hepatocyte Nuclear Factor-3b Gene (HNF3B) in Japanese patients with MODY"Diabetes. 49. 302-305 (2000)

[Publications] Manami Hara: "No diabetes-associated mutations in the coding region of the hepatocyte nuclear factor-4γ (HNF4G) in Japanese patients with MODY"Diabetologia. 43. 1064-1069 (2000)

[Publications] 岩崎直子,岡芳知 編: "糖尿病学2001 2型糖尿病遺伝子カルパイン10-ゲノムワイドスクリーニングの成果と今後の展望"診断と治療社(未確認). (2001)

[Publications] 岩崎直子,春日雅人 編: ""糖尿病"UPDATE糖尿病遺伝子の現況メビオ別冊「Multiple Risk Factor Syndrome」4 Multiple Risk Factorと高血圧"メジカルビュー社. 179 (2000)

[Publications] 岩崎直子,門脇孝 編: "医学のあゆみ第5土曜特集糖尿病の分子医学 ■糖尿病の分子メカニズム2型糖尿病疾患感受性遺伝子"医歯薬出版. 635 (2000)

岩崎直子東京女子医科大学, 医学部, 講師 (70203370)

[Publications] 岩崎直子,岡芳知編: "糖尿病学2001 2型糖尿病遺伝子カルパイン10-ゲノムワイドスクリーニングの成果と今後の展望"診断と治療社(未確認). (2001)

[Publications] 岩崎直子,春日雅人編: ""糖尿病"UPDATE糖尿病遺伝子の現況メビオ別冊「Multiple Risk Factor Syndrome」4 Multiple Risk Factorと高血圧"メジカルビュー社. 179 (2000)

[Publications] 岩崎直子,門脇孝編: "医学のあゆみ第5土曜特集糖尿病の分子医学 ■糖尿病の分子メカニズム2型糖尿病疾患感受性遺伝子"医歯薬出版. 635 (2000)