Mayne Janice, Raymond Angela, Chaplin Anna, Cousins Marion, Kaefer Nadine, Gyamera-Acheampong Charles, Seidah Nabil G, Mbikay Majambu, Chrétien Michel, Ooi Teik Chye
Hormones, Growth and Development Program, Ottawa Health Research Institute, The Ottawa Hospital, University of Ottawa, Ottawa, Ont., Canada.
Biochem Biophys Res Commun. 2007 Sep 21;361(2):451-6. doi: 10.1016/j.bbrc.2007.07.029. Epub 2007 Jul 18.
Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that negatively regulates low density lipoprotein receptor (LDLR) levels. Several single nucleotide polymorphisms (SNPs) in PCSK9 have been linked to autosomal dominant hypercholesterolemia (ADH). Conversely, hypocholesterolemia associates with both 'loss of function' nonsense and missense SNPs in PCSK9. We examined the association of plasma PCSK9 with lipoprotein parameters in 182 normolipidemics. For men (n=98) plasma PCSK9 averaged 6.08+/-1.96 microg/ml and Spearman analysis revealed significant correlation between it and total cholesterol (TC), LDLC, and TC/high density lipoprotein (HDLC) (r=0.276, 0.282, and 0.228, respectively). For women (n=84) plasma PCSK9 averaged 6.46+/-1.99 microg/ml having no correlation with TC, LDLC or TC/HDLC. The ratio of plasma PCSK9/LDLC increased in men carrying 'loss of function' PCSK9 variations. Our results suggest a gender difference in PCSK9 regulation and function with PCSK9 correlated to TC and LDLC in men but not women.
前蛋白转化酶枯草溶菌素9型（PCSK9）是一种分泌型糖蛋白，可负向调节低密度脂蛋白受体（LDLR）水平。PCSK9中的几个单核苷酸多态性（SNP）与常染色体显性高胆固醇血症（ADH）相关。相反，低胆固醇血症与PCSK9中“功能丧失”的无义及错义SNP相关。我们在182名血脂正常者中研究了血浆PCSK9与脂蛋白参数之间的关联。对于男性（n = 98），血浆PCSK9平均为6.08±1.96微克/毫升，Spearman分析显示其与总胆固醇（TC）、低密度脂蛋白胆固醇（LDLC）以及TC/高密度脂蛋白胆固醇（HDLC）之间存在显著相关性（r分别为0.276、0.282和0.228）。对于女性（n = 84），血浆PCSK9平均为6.46±1.99微克/毫升，与TC、LDLC或TC/HDLC无相关性。携带“功能丧失”型PCSK9变异的男性血浆PCSK9/LDLC比值升高。我们的结果表明，PCSK9在调节和功能方面存在性别差异，PCSK9在男性中与TC和LDLC相关，而在女性中则不然。
