Role of single nucleotide polymorphism rs2383206 on coronary artery disease risk among Saudi Population: a case-control study.

OBJECTIVE: We aim to investigate the relationship between genetic variation and biological function on a genomic scale, focusing on identifying genes responsible for complex diseases using single nucleotide polymorphisms. Specifically, the study explores the association between the rs2383206 gene located on chromosome 9p21.3 and the development of coronary artery disease (CAD) in a specific Saudi population. PATIENTS AND METHODS: This case-control study was conducted between September 2013 and May 2015 at King Abdullah Medical City (KAMC) and Al-Noor Specialist Hospital targeting the Saudi Population residing in the western region of Saudi Arabia. The study enrolled 315 cases with documented CAD and 205 controls with normal coronary arteries on coronary angiography. Genomic DNA was extracted from peripheral blood samples of both groups, and genotyping of rs2383206 was performed using the tetra-primer amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) method. RESULTS: In this study, the prevalence of the GG genotype in rs2383206 was found to be higher in patients with CAD than in controls, with an odds ratio of 1.997 [95% confidence interval (CI): 1.176-3.394, p = 0.007]. Additionally, individuals with the GG genotype who had sedentary lifestyles, hyperlipidemia, and smoked were found to be at a higher risk for developing CAD (p = 0.003, 0.009, and 0.003, respectively). The G allele also increased the risk of CAD with an odds ratio of 1.413 (95% CI: 1.099-1.817; p = 0.004). CONCLUSIONS: In conclusion, this study demonstrated a significant association between the rs2383206 variant located on chromosome 9p21 and the development of CAD. The findings of this study provide valuable insights into the genetic susceptibility to CAD and highlight the potential of this variant as a target for future functional studies.

Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy.

AIM: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM. METHODS AND RESULTS: We found that, in ACM patients' explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs. CONTROLS: Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency. CONCLUSIONS: Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients' hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies.