Fathy Shadia A, Abdel Hamid Fatma F, Zabut Baker M, Jamee Amal F, Ali Mohamed A M, Abu Mustafa Ayman M
a Department of Biochemistry , Faculty of Science, Ain Shams University , Cairo , Egypt .
b Biochemistry Department , Faculty of Science, Islamic University , Gaza , Palestine .
Biomarkers. 2015;20(6-7):460-9. doi: 10.3109/1354750X.2015.1093032. Epub 2015 Oct 21.
The number of patients with type 2 diabetes mellitus (T2DM) is progressively increasing, and diabetic cardiovascular complications have become a public health problem. Brain or B-type natriuretic peptide (BNP) is a cardiac hormone synthesized as a pre-pro-peptide. pro-BNP is produced by cleaving the signal peptide then two proprotein convertases, corin and furin cleave pro-BNP to form a biologically active hormone. Two corin single nucleotide polymorphisms (SNPs) have been reported to alter corin protein conformation and impair its biological activity.
We aimed to investigate the potential role of corin and furin in comparison to BNP as biomarkers for predicting cardiovascular complications in T2DM patients. The association of corin gene SNPs with corin levels was also examined.
Seventy-five subjects were recruited in this study, including 25 T2DM patients with complications, 25 T2DM patients without complications as well as 25 healthy subjects. Plasma BNP, corin and furin levels were measured using enzyme-linked immunosorbent assays. Two corin SNPs were genotyped using allele specific oligonucleotide-polymerase chain reaction.
Both furin and BNP were found to be more sensitive than corin (80% versus 56%, p = 0.008), whereas furin showed higher specificity when compared to BNP (96% versus 84%, p = 0.041) and corin (96% versus 64%, p < 0.0001) in predicting cardiovascular complications in T2DM patients. Corin SNPs are not associated with corin levels, neither in the entire study cohort nor in the subgroup of T2DM patients with cardiovascular complications (p > 0.05).
Furin may be useful, either alone or in combination with other biomarkers, for cardiovascular risk stratification assessment in T2DM patients.
2型糖尿病（T2DM）患者数量正在逐步增加，糖尿病心血管并发症已成为一个公共卫生问题。脑钠肽或B型钠尿肽（BNP）是一种以前体前肽形式合成的心脏激素。pro-BNP是通过切割信号肽产生的，然后两种前体蛋白转化酶，即corin和弗林蛋白酶切割pro-BNP形成一种生物活性激素。据报道，两种corin单核苷酸多态性（SNP）会改变corin蛋白构象并损害其生物活性。
我们旨在研究与BNP相比，corin和弗林蛋白酶作为预测T2DM患者心血管并发症生物标志物的潜在作用。还研究了corin基因SNP与corin水平的关联。
本研究招募了75名受试者，包括25名有并发症的T2DM患者、25名无并发症的T2DM患者以及25名健康受试者。使用酶联免疫吸附测定法测量血浆BNP、corin和弗林蛋白酶水平。使用等位基因特异性寡核苷酸聚合酶链反应对两种corin SNP进行基因分型。
在预测T2DM患者心血管并发症方面，发现弗林蛋白酶和BNP都比corin更敏感（分别为80%和56%，p = 0.008），而与BNP（分别为96%和84%，p = 0.041）以及corin（分别为96%和64%，p < 0.0001）相比，弗林蛋白酶显示出更高的特异性。在整个研究队列中以及在有心血管并发症T2DM患者亚组中，corin SNP均与corin水平无关（p > 0.05）。
弗林蛋白酶单独或与其他生物标志物联合使用，可能有助于T2DM患者的心血管风险分层评估。
