Ravi Rowmika, Fernandes Silva Lilian, Vangipurapu Jagadish, Maria Maleeha, Raivo Joose, Helisalmi Seppo, Laakso Markku
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland.
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland.
Metabolites. 2022 May 13;12(5):437. doi: 10.3390/metabo12050437.
Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are among the leading causes of sudden cardiac death. We identified 38 pathogenic or likely pathogenic variant carriers for HCM in three sarcomere genes (, , ) among 9.928 participants of the METSIM Study having whole exome sequencing data available. Eight of them had a clinical diagnosis of HCM. We also identified 20 pathogenic or likely pathogenic variant carriers for DCM in the gene, and six of them had a clinical diagnosis of DCM. The aim of our study was to investigate the metabolite signature in the carriers of the pathogenic or likely pathogenic genetic variants for HCM and DCM, compared to age- and body-mass-index-matched controls. Our novel findings were that the carriers of pathogenic or likely pathogenic variants for HCM had significantly increased concentrations of bradykinin (des-arg 9), vanillactate, and dimethylglycine and decreased concentrations of polysaturated fatty acids (PUFAs) and lysophosphatidylcholines compared with the controls without HCM. Additionally, our novel findings were that the carriers of pathogenic or likely pathogenic variants for DCM had significantly decreased concentrations of 1,5-anhydrogluticol, histidine betaine, N-acetyltryptophan, and methylsuccinate and increased concentrations of trans-4-hydroxyproline compared to the controls without DCM. Our population-based study shows that the metabolite signature of the genetic variants for HCM and DCM includes several novel metabolic pathways not previously described.
肥厚型心肌病（HCM）和扩张型心肌病（DCM）是心源性猝死的主要原因。在METSIM研究中9928名有全外显子测序数据的参与者中，我们在三个肌小节基因（ 、 、 ）中鉴定出38名HCM致病或可能致病的变异携带者。其中8人有HCM临床诊断。我们还在 基因中鉴定出20名DCM致病或可能致病的变异携带者，其中6人有DCM临床诊断。我们研究的目的是，与年龄和体重指数匹配的对照相比，调查HCM和DCM致病或可能致病基因变异携带者的代谢物特征。我们的新发现是，与无HCM的对照相比，HCM致病或可能致病变异的携带者缓激肽（去-精氨酸9）、香草酸和二甲基甘氨酸浓度显著升高，多不饱和脂肪酸（PUFAs）和溶血磷脂酰胆碱浓度降低。此外，我们的新发现是，与无DCM的对照相比，DCM致病或可能致病变异的携带者1,5-脱水葡萄糖醇、组氨酸甜菜碱、N-乙酰色氨酸和甲基琥珀酸浓度显著降低，反式-4-羟基脯氨酸浓度升高。我们基于人群的研究表明，HCM和DCM基因变异的代谢物特征包括几个以前未描述的新代谢途径。
