Ran Zhang1, Yue Zhong1, Si-Yu Long2, Qin-Ni Yang2, Bin Zhou3, Li Rao1. 1. Department of Cardiology, West China Hospital of Sichuan University, Chengdu, China. 2. Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China. 3. Laboratory of Molecular Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Center of Translational Medicine, Ministry of Education, West China Second University Hospital of Sichuan University, Chengdu, China.
Abstract
BACKGROUND: Dilated cardiomyopathy (DCM) is one of the most common types of cardiomyopathies. Various genes have been verified to be related to DCM, but the pathogenesis remains unclear. Cyclin-dependent-kinase 8 (CDK8), encoded by the CDK8 gene, is a transcriptional factor that regulates the phosphorylation of RNA polymerase II. It plays an important role in the transcription process and different signaling pathways. This study aimed to investigate the potential role of CDK8 gene polymorphisms in DCM susceptibility and prognosis in a Chinese Han population. METHODS: Two single nucleotide polymorphisms (SNPs) of CDK8, rs17083838 (A/G) and rs7992670 (A/G), were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 341 DCM patients and 381 healthy controls. Survival analysis was performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: The frequencies of allele A of both SNPs rs17083838 and rs7992670 were increased in DCM patients compared to healthy controls (P<0.05). Genotypic frequencies of rs17083838 and rs7992670 were associated with the susceptibility to DCM in the codominant, and recessive models (P<0.05), and AA/AG genotypes of rs17083838 were also related to DCM susceptibility in the dominant model. AA/AG genotypes of rs17083838 and the AA genotype of rs7992670 in the dominant and recessive genetic models presented a correlation with the poor prognosis of DCM patients in both univariate (P<0.05) and multivariate analyses (P<0.05) after adjusting for age, gender, left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF). CONCLUSIONS: This research is the first to reveal that CDK8 gene polymorphisms might be related to DCM susceptibility and prognosis in the Chinese Han population. 2021 Cardiovascular Diagnosis and Therapy. All rights reserved.
BACKGROUND: Dilated cardiomyopathy (DCM) is one of the most common types of cardiomyopathies. Various genes have been verified to be related to DCM, but the pathogenesis remains unclear. Cyclin-dependent-kinase 8 (CDK8), encoded by the CDK8 gene, is a transcriptional factor that regulates the phosphorylation of RNA polymerase II. It plays an important role in the transcription process and different signaling pathways. This study aimed to investigate the potential role of CDK8 gene polymorphisms in DCM susceptibility and prognosis in a Chinese Han population. METHODS: Two single nucleotide polymorphisms (SNPs) of CDK8, rs17083838 (A/G) and rs7992670 (A/G), were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 341 DCM patients and 381 healthy controls. Survival analysis was performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: The frequencies of allele A of both SNPs rs17083838 and rs7992670 were increased in DCM patients compared to healthy controls (P<0.05). Genotypic frequencies of rs17083838 and rs7992670 were associated with the susceptibility to DCM in the codominant, and recessive models (P<0.05), and AA/AG genotypes of rs17083838 were also related to DCM susceptibility in the dominant model. AA/AG genotypes of rs17083838 and the AA genotype of rs7992670 in the dominant and recessive genetic models presented a correlation with the poor prognosis of DCM patients in both univariate (P<0.05) and multivariate analyses (P<0.05) after adjusting for age, gender, left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF). CONCLUSIONS: This research is the first to reveal that CDK8 gene polymorphisms might be related to DCM susceptibility and prognosis in the Chinese Han population. 2021 Cardiovascular Diagnosis and Therapy. All rights reserved.
Entities:
Keywords:
CDK8; Dilated cardiomyopathy (DCM); polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP); single nucleotide polymorphism (SNP); survival analysis
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