Molecular-genetic analysis of age related hearing impairment

• Project/Area Number: 17390459
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Shinshu University
• Principal Investigator: USAMI Shin-ichi Shinshu University, 医学部, 教授 (10184996)
• Co-Investigator(Kenkyū-buntansha): TAKUMI Yutaka 信州大学, 医学部, 講師 (70312501) ; HIGUCHI Kyouichi 信州大学, 医学系・研究科, 教授 (20173156)
• Co-Investigator(Renkei-kenkyūsha): TAKUMI Yutaka 信州大学, 医学部, 講師 (70312501) ; HIGUCHI Kyouichi 信州大学, 医学系・研究科, 教授 (20173156)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥16,860,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥2,160,000); Fiscal Year 2008: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2007: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥3,900,000 (Direct Cost: ¥3,900,000)
• Keywords: 老人性難聴 / 遺伝子 / 内耳 / 加齢 / SNPs / 聴覚 / 難聴 / 老人 / COL9A3 / CDH23 / SAM / thymosin beta 4 / brain factor 1 / Single minded 2

Research Abstract

高齢化社会の抱える問題の一つとして、老人性難聴によるコミュニケーション障害がある。老人性難聴は、従来から環境要因と遺伝的要因が関与していることが推測されているが、そのメカニズムはほとんど明らかになっていない。本研究では老人性難聴のメカニズムの推定を目的とし、健康な高齢者400名を対象に聴力測定と、候補遺伝子のSNPsの解析を行った。その結果、老人性難聴と有意に相関のある老人性難聴候補遺伝子を2種類見出した。

Research Products

• [Journal Article] Factors that affect hearing level in individuals with the mitochondrial 1555A>G mutation. (2009)
  • Author(s): Ro SY, Nishio s, Tsukada K, Oguchi T, Kobayashi K, Abe S, Usami S.
  • Journal Title: Clinic. Gent (In press)
  • Peer Reviewed
• [Journal Article] The localization of proteins encoded by CRYM, KIAA1199, UBA52, COL9A3, and COL9A1, genes highly expressed in the cochlea (2008)
  • Author(s): Usami S, Takumi Y, Suzuki N, Oguchi T, Oshima A, Suzuki H, Kitoh R, Abe S, Sasaki A, Matsubara A
  • Journal Title: Neuroscience 154(1) Pages: 22-8
  • Peer Reviewed
• [Journal Article] Kimberling WJ.Mutation profile of the CDH23 gene in 56 probands with Usher syndrome type I (2008)
  • Author(s): Oshima A, Jaijo T, Aller E, Millan JM, Carney C, Usami S, Moller C
  • Journal Title: Hum Mutat 29(6)
  • Peer Reviewed
• [Journal Article] The responsible genes in Japanese deafness patients and clinical application using Invader assay (2008)
  • Author(s): Usami S, Wagatsuma M, Fukuoka H, Suzuki H, Tsukada K, Nishio S, Takumi Y, Abe S
  • Journal Title: Acta Otolaryngol 128(4) Pages: 446-54
  • Peer Reviewed
• [Journal Article] The localization of proteins encoded by CRYM, KIAA1199, UBA52, COL9A3, and COL9A1, genes highly expressed in the cochlea. (2008)
  • Author(s): Usami s, Takumi Y, Suzuki N, Oguchi T, Oshima A, Suzuki H, Kitoh R, Abe S, Sasaki A, Matsubara A.
  • Journal Title: Neuroscience 154 Pages: 22-28
  • Peer Reviewed
• [Journal Article] Mutation profile of the CDH23 gene in 56 probands with Usher syndrome type I. (2008)
  • Author(s): Oshima A, Jaijo T, Aller E, Millan JM, Carney C, Usami S, Moller C, Kimberling WJ.
  • Journal Title: Hum Mutat. 29 Pages: 37-46
  • Peer Reviewed
• [Journal Article] The responsible genes in Japanese deafness patients and clinical application using Invader assay (2008)
  • Author(s): Usami S, Wagatsuma M, Fukuoka H, Suzuki H, Tsukada K, Nishio S, Takumi Y, Abe S.
  • Journal Title: Acta Otolaryngol. 128 Pages: 446-454
  • Peer Reviewed
• [Journal Article] micro-Crystallin as an intracellular 3,5,3'-triiodothyronine holder in vivo (2007)
  • Author(s): Suzuki S, Suzuki N, Mori J, Oshima A, Usami S, Hashizume K
  • Journal Title: Mol Endocrinol 21(4) Pages: 885-94
  • Peer Reviewed
• [Journal Article] Phenotypic consequences in a Japanese family having branchio-oto-renal syndrome with a novel frameshift mutation in the gene EYA1 (2007)
  • Author(s): Matsunaga T, Okada M, Usami S, Okuyama T
  • Journal Title: Acta Otolaryngol 127(1) Pages: 98-104
  • Peer Reviewed
• [Journal Article] Application of Deafness Diagnostic Screening Panel Based on Deafness Mutation/Gene Database Using Invader Assay. (2007)
  • Author(s): Abe S, Yamaguchi T, Usami S
  • Journal Title: Genetic Testing 11(3) Pages: 333-340
  • Peer Reviewed
• [Journal Article] Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese (2007)
  • Author(s): Fukuoka H, Kanda Y, Ohta S, Usami S
  • Journal Title: J Hum Genet 52(6) Pages: 510-515
  • Peer Reviewed
• [Journal Article] Immunocytochemical localization of ubiquitin A-52 protein in the mouse inner ear (2007)
  • Author(s): Kitoh R, Oshima A, Suzuki N, Hashimoto S, Takumi Y, Usami S
  • Journal Title: Neuroreport 18(9) Pages: 869-873
  • Peer Reviewed
• [Journal Article] Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss (2007)
  • Author(s): Wagatsuma M, Kitoh R, Suzuki H, Fukuoka H, Takumi Y, Usami S
  • Journal Title: Clin Genet 72(4) Pages: 339-44
  • Peer Reviewed
• [Journal Article] Application of Deafness Diagnostic Screening Panel Based on Deafness Mutation/Gene Database Using Invader Assay. (2007)
  • Author(s): Abe S, Yamaguchi T, Usami S.
  • Journal Title: Genetic Testing 11 Pages: 333-340
  • Peer Reviewed
• [Journal Article] Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese. (2007)
  • Author(s): Fukuoka H, Kanda Y, Ohta S, Usami S.
  • Journal Title: J Hum Genet 52 Pages: 510-515
  • Peer Reviewed
• [Journal Article] Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss. (2007)
  • Author(s): Wagatsuma M, Kitoh R, Suzuki H, Fukuoka H, Takumi Y, Usami S.
  • Journal Title: Clin Genet 72 Pages: 339-344
  • Peer Reviewed
• [Journal Article] Phenotypic consequences in a Japanese family having branchio-oto-renal syndrome with a novel frameshift mutation in the gene EYA1. (2007)
  • Author(s): TATSUO MATSUNAGA, MICHIYO OKADA, SHIN-ICHI USAMI, TORAYUKI OKUYAMA
  • Journal Title: Acta Oto-Laryngologica 127 Pages: 98-104
• [Journal Article] CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea (2006)
  • Author(s): Oshima A, Suzuki S, Takumi Y, Hashizume K, Abe S, Usami S
  • Journal Title: J Med Genet 43(6) Pages: 25-25
  • Peer Reviewed
• [Journal Article] Association of SLC26A4 mutations with clinical features and thyroid function in deaf infants with enlarged vestibular aqueduct (2006)
  • Author(s): Iwasaki S, Tsukamoto K, Usami S, Misawa K, Mizuta K, Mineta H
  • Journal Title: J Hum Genet 51(9) Pages: 805-10
  • Peer Reviewed
• [Journal Article] A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene (2006)
  • Author(s): Van Camp G, Snoeckx RL, Hilgert N, van den Ende J, Fukuoka H, Wagatsuma M, Suzuki H, Smets RM, Vanhoenacker F, Declau F, Van de Heyning P, Usami S
  • Journal Title: Am J Hum Genet 79(3) Pages: 449-57
  • Peer Reviewed
• [Journal Article] Clinical course of hearing and language development in GJB2 and non-GJB2 deafness following habilitation with hearing aids. (2006)
  • Author(s): Matsunaga T, Hirota E, Bito S, Niimi S, Usami S.
  • Journal Title: Audiol Neurootol 11(1) Pages: 59-68
• [Journal Article] CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea. (2006)
  • Author(s): Oshima A, Suzuki S, Takumi Y, Hashizume K, Abe S, Usami S.
  • Journal Title: J Med Genet 43(6):e25
• [Journal Article] Association of SLC26A4 mutations with clinical features and thyroid function in deaf infants with enlarged vestibular Aqueduct. (2006)
  • Author(s): Iwasaki S, Tsukamoto K, Usami S, Misawa K, Mizuta K, Mineta H
  • Journal Title: J Hum Genet e 51(9) Pages: 805-10
• [Journal Article] A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. (2006)
  • Author(s): Van Camp G, Snoeckx RL, Hilgert N, van den Ende J, Fukuoka H, Wagatsuma M, Suzuki H, Smets RM, Vanoenacker F, Declau F, Van de Heyning P, Usami S
  • Journal Title: Am J Hum Genet 79(3) Pages: 449-57
• [Journal Article] 内耳毒性と遺伝子 (2006)
  • Author(s): 宇佐美 真一
  • Journal Title: JOHNS 22:NO.7 Pages: 952-954
• [Journal Article] 難聴診断における遺伝子検査の現状 (2006)
  • Author(s): 宇佐美 真一
  • Journal Title: Audiology Japan 49 Pages: 346-352
  • NAID: 10021298744
• [Journal Article] CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea. (2006)
  • Author(s): Oshima A, Suzuki S, Takumi Y, Hashizume K, Abe S, Usami S.
  • Journal Title: J Med Genet (In press)
• [Journal Article] Clinical course of hearing and language development in GJB2 and non-GJB2 deafness following habilitation with hearing aids (2005)
  • Author(s): Matsunaga T, Hirota E, Bito S, Niimi S, Usami S
  • Journal Title: Audiol Neurootol 11(1) Pages: 59-68
  • Peer Reviewed
• [Journal Article] Genetic diagnosis of deafness. (2005)
  • Author(s): Usami S.
  • Journal Title: Nippon Rinsho 63 Pages: 258-263
  • NAID: 40017119433
• [Journal Article] GABA-induced response in spiral ganglion cells acutely isolated from guinea pig cochlea. (2005)
  • Author(s): Nakagawa T, Yamashita M, Hisashi K, Usami SI.Kakazu Y, Shibata S, Nakashima T, Koike K, Kubo K, Komune S.
  • Journal Title: Neurosci Res 53(4) Pages: 396-403
• [Journal Article] 疾患群の遺伝学的検査と遺伝子検査 難聴 (2005)
  • Author(s): 宇佐美 真一
  • Journal Title: 日本臨床 63 Pages: 258-263
• [Journal Article] Audiological features and mitochondrial DNA sequence in a large family carrying mitochondrial A1555G mutation without use of aminoglycoside. (2005)
  • Author(s): T.Matsunaga, H.Kumanomido, M.Shiroma, Y.Goto, S.Usami.
  • Journal Title: Ann Otol Rhinol Laryngol 114:2 Pages: 153-160
• [Journal Article] Clinical features of patients with GJB2(connexin26) mutations : severity of hearing loss is correlated with genotypes and protein expression patterns. (2005)
  • Author(s): T.Oguchi, A.Ohtsuka S.Hashimoto, A.Oshima S.Abe, Y.Kobayashi, K.Nagai T.Nakagawa, S.Usami
  • Journal Title: J Hum Genet 50 Pages: 76-83
  • NAID: 10014513264
• [Journal Article] Type IX Collagen is crucial for normal hearing (2005)
  • Author(s): K.Asamura, S.Abe Y.Imamura, A.Aszodi N.Suzuki, S.Hashimoto Y.Takumi, T.Hayashi, R.Fassler Y.Nakamura, S.Usami
  • Journal Title: Neuroscience 132 Pages: 493-450
• [Journal Article] Quantitative evaluation of endolymphatic hydrops by bilateral intratympanic Gd-DTPA administration with MRI imaging for Meniere's disease
  • Author(s): Fukuoka H, Tsukada K, Miyagawa M, Oguchi T, Takumi1 Y, Sugiura M, Ueda H, Kadoya M, Usami S
  • Journal Title: Acta Otolaryngol (in press)
  • Peer Reviewed
• [Journal Article] Endolymphatic hydrops and therapeutic effects are visualized in "atypical" Meniere's disease
  • Author(s): Miyagawa M, Fukuoka H, Tsukada K, Oguchi1 T, Takumi Y, Sugiura M, Ueda H, Kadoya M, Usami S
  • Journal Title: Acta Otolaryngol (in press)
  • Peer Reviewed
• [Journal Article] Factors that affect hearing level in individuals with the mitochondrial 1555A>G mutation Clinic
  • Author(s): Ro SY, Nishio S, Tsukada K, Oguchi T, Kobayashi K, Abe S, Usami S
  • Journal Title: Gent. 2008 (in press)
  • Peer Reviewed
• [Presentation] SNP frequency in COCH is involved in Age-Related Hearing Impairment in aged Japanese (2009)
  • Author(s): Hashimoto S, Shinshu University Gene Research Consortium, NPO JTR, Nishio S, Takumi Y, Usami S
  • Organizer: 第3回運動・遺伝子・予防医療国際シンポジウム
  • Place of Presentation: 松本
  • Year and Date: 2009-03-16
• [Presentation] SNP frequency in COCH is involved in Age-Related Hearing Impairment in aged Japanese (2009)
  • Author(s): Shigenari Hashimoto, Shinshu University Gene Research Consortium, NPO JTR, Shin-ya Nishio, Yutaka Takumi, Shin-ichi Usami
  • Organizer: 「運動・遺伝子・予防医療」第3回国際シンポジウム
  • Place of Presentation: 松本
  • Year and Date: 2009-03-16
• [Presentation] Shinshu University Gene Research Consortium, NPO JTR, Nishio S, Takumi Y, Usami S, SNP frequency in COCH is involved in Age-Related Hearing Impairment in aged Japanese (2009)
  • Author(s): Hashimoto S
  • Organizer: 第2回運動・遺伝子・予防医療国際シンポジウム
  • Place of Presentation: 松本
  • Year and Date: 2009-03-11
• [Presentation] 老人性難聴における遺伝的素因の検討 : セカンドコホートでの解析およびプロモーター領域の検討 (2008)
  • Author(s): 橋本繁成, 鈴木伸嘉, 工穣, 宇佐美真一
  • Organizer: 第回18日本耳科学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2008-10-18
• [Presentation] 老人性難聴における遺伝的素因の検討 : セカンドコホートでの解析およびプロモーター領域の検討 (2008)
  • Author(s): 橋本繁成, 鈴木伸嘉, 工穣, 宇佐美真一
  • Organizer: 第18回日本耳科学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2008-10-18
• [Presentation] 老人性難聴における遺伝的因子の関与について-老人性難聴候補遺伝子のSNP遺伝子型と聴力との相関解析- (2007)
  • Author(s): 橋本繁成, 鈴木伸嘉, 工穣, 宇佐美真一
  • Organizer: 第17回日本耳科学会
  • Place of Presentation: 福岡
  • Year and Date: 2007-10-19
• [Presentation] SAM の内耳における遺伝子発現について (2007)
  • Author(s): 鈴木伸嘉, 橋本繁成, 工穣, 宇佐美真一
  • Organizer: 第17回日本耳科学会
  • Place of Presentation: 福岡
  • Year and Date: 2007-10-18
• [Presentation] SAMの内耳における遺伝子発現について (2007)
  • Author(s): 鈴木伸嘉, 橋本繁成, 工穣, 宇佐美真一
  • Organizer: 第22回老化促進モデルマウス(SAM)研究協議会
  • Place of Presentation: 山形
  • Year and Date: 2007-07-26
• [Presentation] Gene expression profiles in the cochlea of the senescence-accelerated mouse (SAM) (2007)
  • Author(s): 鈴木伸嘉, 橋本繁成, 工穣, 宇佐美真一
  • Organizer: 国際老人性難聴会議
  • Place of Presentation: ベルギー
  • Year and Date: 2007-05-25
• [Presentation] SNP frequency in COCH is involved in Age-Related Hearing Impairment in aged Japanese (2007)
  • Author(s): 橋本繁成, 鈴木伸嘉, 工穣, 宇佐美真一
  • Organizer: 国際老人性難聴会議
  • Place of Presentation: ベルギー
  • Year and Date: 2007-05-23
• [Presentation] Gene expression profiles in the cochlea of the senescence-accelerated mouse(SAM) (2007)
  • Author(s): 鈴木伸嘉
  • Organizer: 国際老人性難聴会議
  • Place of Presentation: ベルギー
• [Presentation] SAMの内耳における遺伝子発現について (2007)
  • Author(s): 鈴木伸嘉
  • Organizer: 第17回日本耳科学会
  • Place of Presentation: 福岡
• [Presentation] 老人性難聴における遺伝的因子の関与について -老人性難聴候補遺伝子のSNP遺伝子型と聴力との相関解析- (2007)
  • Author(s): 橋本繁成
  • Organizer: 第17回日本耳科学会
  • Place of Presentation: 福岡
• [Remarks] 市民公開講座宇佐美真一, 耳の日市民公開講座「老人性難聴研究の進歩」, 2008.3.1, 長野