Department of Internal Medicine, Division of Cardiology, Henry Ford Heart and Vascular Institute, Henry Ford Hospital, Detroit, MI, USA,
J Cardiovasc Transl Res. 2013 Oct;6(5):826-33. doi: 10.1007/s12265-013-9491-y. Epub 2013 Jul 9.
The natriuretic peptide (NP) system is a critical physiologic pathway in heart failure with wide individual variability in functioning. We investigated the genetic component by testing the association of single nucleotide polymorphisms (SNP) with RNA and protein expression. Samples of DNA, RNA, and tissue from human kidney (n = 103) underwent genotyping, RT-PCR, and protein quantitation (in lysates), for four candidate genes [NP receptor 1 (NPR1), NPR2, and NPR3 and membrane metalloendopeptidase]. The association of genetic variation with expression was tested using linear regression for individual SNPs, and a principal components (PC) method for overall gene variation. Eleven SNPs in NPR2 were significantly associated with protein expression (false discovery rate ≤0.05), but not RNA quantity. RNA and protein quantity correlated poorly with each other. The PC analysis showed only NPR2 as significant. Assessment of the clinical impact of NPR2 genetic variation is needed.
利钠肽（NP）系统是心力衰竭中一个关键的生理途径，其功能存在广泛的个体差异。我们通过检测单核苷酸多态性（SNP）与 RNA 和蛋白质表达的关联来研究遗传成分。对来自人类肾脏的 DNA、RNA 和组织样本（n=103）进行基因分型、RT-PCR 和蛋白质定量（在裂解物中），针对四个候选基因 [NP 受体 1（NPR1）、NPR2 和 NPR3 和膜金属内肽酶]。使用线性回归测试个体 SNP 与表达的关联，以及主成分（PC）方法测试整体基因变异。NPR2 中的 11 个 SNP 与蛋白表达显著相关（错误发现率≤0.05），但与 RNA 量无关。RNA 和蛋白质数量彼此之间相关性较差。PC 分析仅显示 NPR2 有意义。需要评估 NPR2 遗传变异的临床影响。
