The pharmacologic inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) lowers lipoprotein (a) [Lp(a)] concentrations. However, the impact of genetic PCSK9 loss-of-function variants (LOFVs) on Lp(a) is uncertain. We determined the association of PCSK9 LOFVs with Lp(a) measures among black adults. Genotyping for PCSK9 LOFVs was conducted in 10,196 black Reasons for Geographic and Racial Differences in Stroke study participants. Among 241 participants with and 723 randomly selected participants without PCSK9 LOFVs, Lp(a) concentations, apo(a) kringle IV (KIV) repeats (a proxy for isoform size), and oxidized phospholipid (OxPL) apoB levels were measured using validated methods. Median Lp(a) concentrations among participants with and without PCSK9 LOFVs were 63.2 and 80.4 nmol/l, respectively (P = 0.016). After adjusting for age, sex, estimated glomerular filtration rate, LDL cholesterol, and statin use, participants with versus without a PCSK9 LOFV had a lower median Lp(a) concentration [Δ = -18.8 nmol/l (95% CI: -34.2, -3.3)]. Median apo(a) isoform sizes were 24 and 23 KIV repeats (P = 0.12) among participants with and without PCSK9 LOFVs, respectively [Δ = 1.1 (95% CI: 0.2, 2.0) after adjustment]. Median OxPL-apoB levels among participants with and without PCSK9 LOFVs were 3.4 and 4.1 nM (P = 0.20), respectively [Δ = -1.2 nM (95% CI -2.4, -0.04) after adjustment]. Among black adults, PCSK9 LOFVs were associated with lower Lp(a) concentration and OxPL-apoB levels.

中文翻译：

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美国黑人成年人中PCSK9功能丧失的变异和Lp（a）表型。

9型前蛋白转化酶枯草杆菌蛋白酶-kexin（PCSK9）的药理抑制作用降低了脂蛋白（a）[Lp（a）]的浓度。但是，遗传PCSK9功能丧失变异（LOFV）对Lp（a）的影响尚不确定。我们确定了PCSK9 LOFV与黑人成年人中Lp（a）量度的关联。对PCSK9 LOFV进行基因分型的研究对象为10,196名卒中研究参与者的地理和种族差异的黑色原因。在使用PCSK9 LOFV的241名参与者和723名随机选择的参与者中，使用经过验证的方法测量了Lp（a）浓度，apo（a）克林格IV（KIV）重复序列（同工型大小的替代物）和氧化磷脂（OxPL）apoB的水平。有和没有PCSK9 LOFV的参与者中Lp（a）的中位数浓度分别为63.2和80.4 nmol / l（P= 0.016）。在调整了年龄，性别，估计的肾小球滤过率，LDL胆固醇和他汀类药物使用后，有或没有PCSK9 LOFV的参与者的Lp（a）浓度中位数较低[Δ= -18.8 nmol / l（95％CI：-34.2 ，-3.3）]。在有和没有PCSK9 LOFV的参与者中，平均apo（a）同工型大小分别为24和23 KIV重复（P = 0.12）[调整后Δ= 1.1（95％CI：0.2，2.0）。有和没有PCSK9 LOFV的参与者之间的OxPL-apoB水平中位数分别为3.4和4.1 nM（P = 0.20）[调整后的Δ= -1.2 nM（95％CI -2.4，-0.04）]。在黑人成年人中，PCSK9 LOFV与较低的Lp（a）浓度和OxPL-apoB水平相关。