Abifadel Marianne, Varret Mathilde, Rabès Jean-Pierre, Allard Delphine, Ouguerram Khadija, Devillers Martine, Cruaud Corinne, Benjannet Suzanne, Wickham Louise, Erlich Danièle, Derré Aurélie, Villéger Ludovic, Farnier Michel, Beucler Isabel, Bruckert Eric, Chambaz Jean, Chanu Bernard, Lecerf Jean-Michel, Luc Gerald, Moulin Philippe, Weissenbach Jean, Prat Annick, Krempf Michel, Junien Claudine, Seidah Nabil G, Boileau Catherine
INSERM U383, Hôpital Necker-Enfants Malades, AP-HP, Université Paris V, 149-161 rue de Sèvres, 75743 Paris Cedex 15, France.
Nat Genet. 2003 Jun;34(2):154-6. doi: 10.1038/ng1161.
Autosomal dominant hypercholesterolemia (ADH; OMIM144400), a risk factor for coronary heart disease, is characterized by an increase in low-density lipoprotein cholesterol levels that is associated with mutations in the genes LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B). We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH. PCSK9 encodes NARC-1 (neural apoptosis regulated convertase), a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis.
常染色体显性高胆固醇血症（ADH；OMIM144400）是冠心病的一个风险因素，其特征是低密度脂蛋白胆固醇水平升高，这与低密度脂蛋白受体（LDLR）基因（编码低密度脂蛋白受体）或载脂蛋白B（APOB）基因（编码载脂蛋白B）的突变有关。我们在1p32定位了与ADH相关的第三个基因座HCHOLA3，现在报告了导致ADH的前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）基因中的两个突变。PCSK9编码NARC-1（神经细胞凋亡调节转化酶），这是一种新发现的人类枯草杆菌蛋白酶，在肝脏中高度表达并有助于胆固醇稳态。
