| Project/Area Number |
12357016
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Kyorin University |
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Principal Investigator |
ENDOU Hitoshi Kyorin Univ. School of Medicine, Professor, 医学部, 教授 (20101115)
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| Co-Investigator(Kenkyū-buntansha) |
HOSOYAMDA Makoto Kyorin Univ. School of Medicine, Lecturer, 医学部, 講師 (00291659)
TAKEDA Michio Kyorin Univ. School of Medicine, Associate Professor, 医学部, 助教授 (40255401)
KNAI Yoshikatsu Kyorin Univ. School of Medicine, Professor, 医学部, 教授 (60204533)
ANZAI Naohiko Kyorin Univ. School of Medicine, Assistant, 医学部, 助手 (70276054)
KIM Dokyung Kyorin Univ. School of Medicine, Assistant, 医学部, 助手 (40327474)
稲富 淳 杏林大学, 医学部, 助手 (00311960)
車 碩鎬 杏林大学, 医学部, 助手 (50276200)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥43,160,000 (Direct Cost: ¥39,800,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2002: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2001: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2000: ¥28,600,000 (Direct Cost: ¥28,600,000)
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| Keywords | Anion transporter / Cation transporter / Carnitine / Idopathic renal hypouricemia / Uric acid / SNP / Epididymis / Sertoli cell / 胎盤 / 突発性腎性低尿酸血症 / パラアミノ馬尿酸 / 一塩基変異遺伝子多型 / イントロン / エクソン / エストロン硫酸 / デヒドロエピアンドロステロン硫酸 |
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| Research Abstract |
Molecular identification of new members
Within the last three years, the following genes have been newly identified.
Organic anion transporters (SLC 22): Organic anion transporter 4 (OA4) in 2000, Urate transporter 1 (URAT1) in 2002, Carnitine transporter 2 (CT2) in 2002
Heterodimeric amino acid transporters (SLC 7): Asc-type amino acid transporter 1 (Asc1) in 2000, Asc-type amino acid transporter 2 (Asc2) in 2001, Asparate/glutamate transporter 1 (AGT1) in 2002
Choline transporter (SLC 5): High affinity choline transpoter 1(CHT1) in 2000
Sodium-independent aromatic amino acid transporter (SLC 6): T-type amino acid transporter 1 (TAT1) in 2001
In addition to molecular cloning of the new members stated above, we have characterized intensively our already cloned members including OAT1, OAT2, OAT3, LAT1, LAT2, BAT1, NBC-1, GLAST and Nramp2. The new members like URAT1 and CT2 are typical examples of "dry cloning" strategy.
Genetic polymorphism of transporters
Individual variations of pharmacokinet
… More
ics and toxicokinetics are new issues to be carried out successful and clearcut results was discovery of URAT1 and its mutants. Idiopathic renal hypouricemia could be explained by URAT1 mutations. Until now, more than 90% of these clinical cases showed URAT1 mutation. Thus, major cause of this abnormality cn be explained as URAT1 polymorphism. Minor components, however, may include different pathogenesis like URAT2 that has never been identified yet.
Similar to URAT1 in idiopathic renal hypouricemia, cystinuria could be demonstrated by either B-type amino acid transporter 1 (BAT 1) abnormality or related BAT (rBAT) polymorphism. There can be seen minor cases having wild type of BAT1 and rBAT suggesting that there should be additional components like BAT2 etc. Further efforts, therefore, are needed to explain fully the real causes of cystinuria.
Single nucleotide polymorphism (SNP) strategy is becoming important to understand to understand individual variation of pharmacokinetics and tailor-made therapeutic strategy. A member of SLC 22, organic cation transporter 2 (OCT2) reveals relatively high frequency of genetic polymorphism. On the other hand, organic anion transporters (OATs) show rarely polymorphism. Although this project has been terminated, this kind of approaches is inevitable to extend transporter researches close to clinical studies. Less
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