臨床眼科63巻11号

2009年10月発行

特集 緑内障診療―グレーゾーンを越えて

Ⅰ．診断編 6．疫学調査と遺伝

遺伝解析の現状

著者： 布施昇男¹

所属機関： ¹東北大学大学院医学系研究科感覚器病態学講座眼科学部門

ページ範囲：P.200 - P.209

文献概要

はじめに

　現在わが国における40歳以上の緑内障有病率は5％とされ，人口から概算して緑内障患者は約200万人にものぼると推定される。病型別にみてみると，わが国においては正常眼圧緑内障（normal-tension glaucoma：NTG）が，原発開放隅角緑内障（狭義）（primary open-angle glaucoma：POAG）に対し10倍以上の頻度で存在する。とくに原発開放隅角緑内障，正常眼圧緑内障に関しては，環境因子の関与や浸透率の低さなどから一般的な病気（common disease）と考えられる。

　近年，common diseaseに関しては次々に新しい知見が発表されている。眼科領域では，加齢黄斑変性や落屑症候群，落屑緑内障と強く相関する遺伝子が発表された。加齢黄斑変性は高齢者で発症するが，環境因子と遺伝因子の双方が関連するcommon diseaseと考えられる。2005年に補体H因子（CFH）遺伝子^1～3）が，続いて2006年にセリンプロテアーゼであるHTRA1のプロモーター領域の一塩基多型（single nucleotide polymorphism：SNP）^4）が，加齢黄斑変性の発症に大きく相関していることが発表された。2007年には，Thorleifssonら^5）によるゲノムワイドな解析により，常染色体15番長腕に位置するLOXL1遺伝子のエクソン1およびイントロン1内に存在する計3つの一塩基多型が，落屑症候群，落屑緑内障と強く相関すると発表された。

　このように，近年common diseaseの解析が相次いでなされているが，原発開放隅角緑内障，正常眼圧緑内障に関してはいまだもって解析は発展途上であり，グレーゾーンが非常に大きい。今回は，緑内障遺伝解析の現状を概観し，将来にかけて越えるべきグレーゾーンを俯瞰してみたい。

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