{"created":"2023-07-27T06:54:56.384230+00:00","id":50526,"links":{},"metadata":{"_buckets":{"deposit":"cb504a83-ecbd-4974-8fd7-9836494adeec"},"_deposit":{"created_by":18,"id":"50526","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"50526"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00050526","sets":["2812:2813:2827"]},"author_link":["91478","381"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2007-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"3p.","bibliographicVolumeNumber":"2005-2006","bibliographic_titles":[{"bibliographic_title":"平成18(2006)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2006 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"プロスタグランジン関連薬であるラタノプロストは、眼圧下降薬として広く用いられているが、その眼圧下降作用には個人差があることが知られている。現時点では何が個人による眼圧下降作用を規定しているかは明らかではない。そこで、我々は健常人を対象に、ラタノプロスト点眼による眼圧下降作用と、ラタノプロストに高い親和性を持つプロスタグランジンFαレセプター(FPレセプター)遺伝子の多型(Single Nucleotide Polymorphism : SNP)に関連性があるかどうかを検討した。\nFPレセプター遺伝子のSNPを主にダイレクトシークエンスにより探索し、タイピングした。その結果10個のSNPが検出された。健常人100人に対して、ラタノプロストを片眼に1日1回7日間点眼し、7日後の眼圧下降率を他眼を対照として算出した。眼圧下降率はFPレセプター遺伝子のプロモーター領域のSNP(rs3753380)において、C/Cホモの眼圧下降率は20.3±1.5%(平均±標準誤差)(n=52)、Tキャリアー(C/T+T/T)は15.6±1.2%(n=48)と有意な差があった(P<0.05)。他の多型に関しては遺伝子型と眼圧下降率に有意な関連はみられなかった。しかし、眼圧下降率により被験者をロー-、ミディアム-、ハイ-レスポンダーと分類し、各遺伝子型と解析すると、第一イントロンにあるrs3766355と眼圧下降作用の間にも関連性が見出された。また、FPレセプター遺伝子のプロモーター領域を、ホタルのルシフェラーゼ遺伝子の上流に連結し、レポーターアッセイを行った。その結果、rs3766355がCでrs3753380がTであると、ルシフエラーゼの活性が低下した。\n以上より、FPレセプター遺伝子のプロモーター(rs3753380)と第一イントロン(rs3766355)の多型がラタノプロストによる眼圧下降の個人差を引き起こす一つの要因である可能性が示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"Latanoprost, a prostaglandin F2o analogue, is widely used to lower the intraocular pressure (10P) in patients with glaucoma although in some cases the response is unexpectedly weak. It is currently unknown what is responsible for the weak responses to latanoprost in different patients. We attempted to evaluate the relationship between polymorphisms of the prostaglandin F2n receptor (FP receptor) gene and the effectiveness of topical latanoprost treatment in normal volunteers.\nSingle nucleotide polymorphisms (SNPs) in the FP receptor gene were searched and the genotype was determined mainly by direct DNA sequencing. Ten SNPs were identified in this study. Baseline IOPs of both eyes of 100 normal subjects were measured at three time points. Latanoprost (0.005%) was applied to one eye once daily, for 7 days. Diurnal 10P was measured again on day 7. Response to latanoprost was evaluated by percent 10P reduction in the treated eye minus 10P fluctuations of the non-treated eye. One SNP, rs375 3380, was located in the promoter region of the FP receptor gene and was significantly correlated with the mean diurnal percent 10P reduction (%AIOP) (CC, 20.3 ± 1.5% (mean ± SEM); CT + TT, 15.6 ± 1.2%, P = 0.0316). The %AIOP was not correlated with other SNPs. We classified subjects by the %ΔI0P into 3 groups: low-responders (%ΔIOP <10%), medium-responders (10%<%ΔIOP <25%), and high-responders (%Δ10P<25%). When the category classified by the %oIOP was analyzed, not only rs3753380 but also rs3766355, a SNP in intron 1, were associated with the degree of response to latanoprost. A promoter assay with a reporter luciferase gene revealed that the C allele of rs3766355 and T allele of rs3753380 were found in constructs with lower transcriptional activity of the FP receptor gene.\nrs3753380 and rs3766355, SNPs in the promoter and intron 1 regions of the FP receptor gene, correlate with a response to short-term latanoprost treatment in normal volunteers. The genotype of these SNPs may be an important determinant of variability in response to latanoprost.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:17591826, 研究期間(年度):2005-2006","subitem_description_type":"Other"},{"subitem_description":"出典：「ラタノプロストの眼圧下降作用を規定する遺伝子多型の解析」研究成果報告書　課題番号17591826\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00056835","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学附属病院"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=50303269"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=50303269","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591826/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591826/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17591826/175918262006kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17591826/175918262006kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-02-07"}],"displaytype":"detail","filename":"HO-PR-SAKURAI-M-kaken 2007-3p.pdf","filesize":[{"value":"100.4 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"HO-PR-SAKURAI-M-kaken 2007-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/50526/files/HO-PR-SAKURAI-M-kaken 2007-3p.pdf"},"version_id":"9fc54a10-25b8-44cd-aa0a-e004c96581b6"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"ラタノプロストの眼圧下降作用を規定する遺伝子多型の解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"ラタノプロストの眼圧下降作用を規定する遺伝子多型の解析"},{"subitem_title":"Analysis of association between genetic polymorphisms of the prostaglandin F2 IA receptor gene and response to latanoprost","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2827"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-02-07"},"publish_date":"2020-02-07","publish_status":"0","recid":"50526","relation_version_is_last":true,"title":["ラタノプロストの眼圧下降作用を規定する遺伝子多型の解析"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:33:46.575529+00:00"}