Genetic Polymorphisms of FCGRT Encoding FcRn in a Japanese Population and Their Functional Analysis

被引：20

作者：

Ishii-Watabe, Akiko ^{[2
]}

Saito, Yoshiro ^{[1
,3
]}

Suzuki, Takuo ^{[2
]}

Tada, Minoru ^{[2
]}

Ukaji, Maho ^{[3
]}

Maekawa, Keiko ^{[3
]}

Kurose, Kouichi ^{[3
]}

Kaniwa, Nahoko ^{[3
]}

Sawada, Jun-ichi ^{[3
,4
]}

Kawasaki, Nana ^{[2
]}

Yamaguchi, Teruhide ^{[2
]}

Nakajima, Takako Eguchi ^{[5
]}

Kato, Ken ^{[5
]}

Yamada, Yasuhide ^{[5
]}

Shimada, Yasuhiro ^{[5
]}

Yoshida, Teruhiko ^{[6
]}

Ura, Takashi ^{[7
]}

Saito, Miyuki ^{[7
]}

Muro, Kei ^{[7
]}

Doi, Toshihiko ^{[8
]}

Fuse, Nozomu ^{[8
]}

Yoshino, Takayuki ^{[8
]}

Ohtsu, Atsushi ^{[8
,9
]}

Saijo, Nagahiro

Hamaguchi, Tetsuya ^{[5
]}

Okuda, Haruhiro ^{[3
,4
]}

Matsumura, Yasuhiro ^{[10
]}

机构：

[1] Natl Inst Hlth Sci, Div Med Safety Sci, Setagaya Ku, Tokyo 1588501, Japan

[2] Natl Inst Hlth Sci, Div Biol Chem & Biol, Tokyo 1588501, Japan

[3] Natl Inst Hlth Sci, Project Team Pharmacogenet, Tokyo 1588501, Japan

[4] Natl Inst Hlth Sci, Div Organ Chem, Tokyo 1588501, Japan

[5] Natl Canc Ctr, Gastrointestinal Oncol Div, Tokyo, Japan

[6] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 104, Japan

[7] Aichi Canc Ctr Hosp, Dept Med Oncol, Nagoya, Aichi 464, Japan

[8] Natl Canc Ctr Hosp E, Div Gastrointestinal Oncol Digest Endoscopy, Kashiwa, Chiba, Japan

[9] Natl Canc Ctr Hosp E, Res Ctr Innovat Oncol, Kashiwa, Chiba, Japan

[10] Natl Canc Ctr Hosp E, Invest Treatment Div, Kashiwa, Chiba, Japan

来源：

DRUG METABOLISM AND PHARMACOKINETICS | 2010年 / 25卷 / 06期

基金：

日本学术振兴会;

关键词：

FCGRT; neonatal Fc receptor (FcRn); genetic polymorphism; novel non-synonymous variation; MONOCLONAL-ANTIBODIES; FUSION PROTEINS; IGG BINDING; RECEPTOR; PHARMACOKINETICS; CELLS; BETA(2)-MICROGLOBULIN; EXOCYTOSIS; EXPRESSION;

D O I：

10.2133/dmpk.DMPK-10-RG-067

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Neonatal Fc receptor (FcRn) plays an important role in regulating IgG homeostasis in the body. Changes in FcRn expression levels or activity caused by genetic polymorphisms of FCGRT, which encodes FcRn, may lead to interindividual differences in pharmacokinetics of therapeutic antibodies. In this study, we sequenced the 5'-flanking region, all exons and their flanking regions of FCGRT from 126 Japanese subjects. Thirty-three genetic variations, including 17 novel ones, were found. Of these, two novel non-synonymous variations, 629G > A (R210Q) and 889T > A (S297T), were found as heterozygous variations. We next assessed the functional significance of the two novel non-synonymous variations by expressing wild-type and variant proteins in HeLa cells. Both variant proteins showed similar intracellular localization as well as antibody recycling efficiencies. These results suggested that at least no common functional polymorphic site with amino acid change was present in the FCGRT of our Japanese population.

引用

页码：578 / 587

页数：10

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