BRAIN and NERVE－神経研究の進歩60巻11号

2008年11月発行

特集 脳卒中と遺伝子

高リポ蛋白(a)血症とアポリポ蛋白(a)遺伝子多型

著者： 一瀬白帝¹

所属機関： ¹山形大学医学部器官病態統御学

ページ範囲：P.1307 - P.1317

文献概要

はじめに

　21世紀は血栓症の時代である。心筋梗塞と脳梗塞を合わせた血管病は，がんと並んでわが国の死亡原因の約3割を占めており，現在も増加しつつある。脳卒中の多くは虚血性脳血管障害であり，動脈硬化性（大血管病），心原性塞栓性，ラクナ性（小血管病），原因不明などに分類されるが，多遺伝子病，単一遺伝子病，多因子疾患の不均一な集合である。年齢，高血圧，糖尿病，喫煙，肥満，脂質異常症，虚血性心血管病，心不全，心房細動，運動不足などの古典的な危険因子に加えて，それらに影響したり，血栓形成の前段階である動脈硬化に直接関与したり，各種の環境因子と相互作用したりする遺伝因子が，脳梗塞の危険因子として重要である。特に，炎症，血液凝固や血管壁の成分の異常，代謝の障害を起きやすくするような遺伝子変異や多型性は，発症頻度の高さ，発症年齢の若さと相関している。これらのうち，向血栓性あるいは血栓傾向は，凝固系，線溶系，血小板，血管内皮細胞の変調をきたす遺伝子変異や多型性によって惹起される（文献1の表1，2を参照）。

　まず，凝固系では凝固V因子Leiden変異（Arg506Gln），プロトロンビン遺伝子3'領域多型（G20210A），フィブリノーゲンβ鎖遺伝子5'発現調節領域多型（G-455A），XIII因子Val34Leu多型などが脳梗塞の危険因子であるが，β鎖G-455A以外は日本人を含むモンゴロイドには存在しない。抗凝固系では，アンチトロンビン，プロテインC，Sの欠損や多型，トロンボモジュリンAla455Val多型，血小板では糖蛋白質GPIbαのMet145Thr多型，GPIIIaのLeu33Pro多型などが血栓症と相関することが知られている。線溶系ではプラスミノゲンアクチベーターインヒビタータイプ1遺伝子の5'発現調節領域の縦列繰り返し配列多型（4G/5G-675）と，アポリポプロテイン（a）［以後，アポ（a）］遺伝子のクリングルドメインの数とアミノ酸配列，5'発現調節領域の多型が，それぞれの遺伝子産物を増加させる重要な危険因子である。本稿では，後者のアポ（a）遺伝子と脳梗塞の関係について述べる。

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