Department of Lipidology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Atherosclerosis. 2011 Feb;214(2):404-7. doi: 10.1016/j.atherosclerosis.2010.11.005. Epub 2010 Nov 13.
Familial hypercholesterolemia (FH) is caused by mutations of FH genes, i.e. LDL-receptor (LDLR), PCSK9 and apolipoprotein B (ApoB) gene. We evaluated the usefulness of DNA analysis for the diagnosis of homozygous FH (homo-FH), and studied the frequency of FH in the Hokuriku district of Japan.
Twenty-five homo-FH patients were recruited. LDLR mutations were identified using the Invader assay method. Mutations in PCSK9 were detected by PCR-SSCP followed by direct sequence analysis.
We confirmed 15 true homozygotes and 10 compound heterozygotes for LDLR mutations. Three types of double heterozygotes for LDLR and PCSK9 were found. No FH patients due to ApoB mutations were found. The incidences of homo-FH and hetero-FH in the Hokuriku district were 1/171,167 and 1/208, respectively.
Our observations underlined the value of FH gene analysis in diagnosing homo-FH and confirmed extraordinarily high frequency of FH in the Hokuriku district of Japan.
家族性高胆固醇血症（FH）是由 FH 基因，即 LDL 受体（LDLR）、前蛋白转化酶枯草溶菌素 9（PCSK9）和载脂蛋白 B（ApoB）基因突变引起的。我们评估了 DNA 分析在诊断纯合子家族性高胆固醇血症（homo-FH）中的作用，并研究了日本北陆地区 FH 的频率。
招募了 25 名 homo-FH 患者。使用 Invader 检测方法鉴定 LDLR 突变。通过 PCR-SSCP 检测 PCSK9 突变，然后直接进行序列分析。
我们证实了 15 例 LDLR 突变的真正纯合子和 10 例复合杂合子。发现了 3 种 LDLR 和 PCSK9 的双杂合子。未发现 ApoB 突变导致的 FH 患者。北陆地区 homo-FH 和 hetero-FH 的发病率分别为 1/171167 和 1/208。
我们的观察结果强调了 FH 基因分析在诊断 homo-FH 中的价值，并证实了日本北陆地区 FH 的极高发病率。
