γGT 和载脂蛋白 B 代谢关键酶（PCSK9）基因变异在高 LDL-胆固醇血症患者中的作用。
γGT and PCSK9 variants in subjects with hyper-LDL-cholesterolemia.
机构信息
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Jichi Medical University.
出版信息
Acta Biomed. 2022 Dec 16;93(6):e2022314. doi: 10.23750/abm.v93i6.13357.
BACKGROUND AND AIM
Gain-of-function (GOF) variants of proprotein convertase subtilisin/kexin type 9 (PCSK9) gene cause high blood low-density lipoprotein (LDL) cholesterol and PCSK9 levels, which are respectively the markers of cardiovascular disease (CVD). High blood activity of gamma-glutamyl transpeptidase (γGT), a pro-oxidant induced by oxidative conditions, is also a marker of CVD. There may be an association between γGT and PCSK9 variants. We aimed to examine the γGT activity by a GOF variant, p.E32K, of PCSK9 in subjects with hyper-LDL-cholesterolemia, an at-risk state for CVD.
METHODS
This study enrolled 114 subjects (mean age, 59 years; 38 males) with hyper-LDL-cholesterolemia who underwent a genotype assay for identification of p.E32K variant and enzymatic measurement of γGT activity. The relationship between the γGT activity and p.E32K was analyzed.
RESULTS
γGT activity was significantly lower (median, 21 IU/L) in subjects with p.E32K (n = 12) than in those without the variant (30 IU/L, P < 0.05). The results remained confirmed by multivariate-adjusted analysis.
CONCLUSIONS
An inverse association was found between γGT and p.E32K, a GOF variant. Elucidation of the mechanism for their association may help understand the development of CVD by PCSK9 variants.
背景与目的
前蛋白转化酶枯草溶菌素/胰凝乳蛋白酶 9（PCSK9）基因的获得性功能（GOF）变异可导致血液中低密度脂蛋白（LDL）胆固醇和 PCSK9 水平升高，这分别是心血管疾病（CVD）的标志物。γ-谷氨酰转肽酶（γGT）的血液活性升高，这是一种由氧化条件诱导的促氧化剂，也是 CVD 的标志物。γGT 与 PCSK9 变异之间可能存在关联。我们旨在检查高 LDL-胆固醇血症患者中 PCSK9 的 GOF 变异 p.E32K 对 γGT 活性的影响，高 LDL-胆固醇血症是 CVD 的高危状态。
方法
这项研究纳入了 114 名患有高 LDL-胆固醇血症的受试者（平均年龄 59 岁；38 名男性），他们接受了 p.E32K 变异的基因检测和 γGT 活性的酶学测量。分析了 γGT 活性与 p.E32K 之间的关系。
结果
p.E32K 变异组（n = 12）的 γGT 活性显著降低（中位数 21 IU/L），而无该变异组的 γGT 活性为 30 IU/L（P < 0.05）。多变量调整分析的结果也得到了确认。
结论
发现 γGT 与 PCSK9 的 GOF 变异 p.E32K 之间存在负相关。阐明它们之间的关联机制可能有助于了解 PCSK9 变异导致 CVD 的发生机制。
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