The study of copy number variations in the regions of PRKAB2 and PPM1K among congenital heart defects patients

Abstract

SUMMARY OBJECTIVE: This study was to assess the genetic association of copy number variations in two genes (PRKAB2 and PPM1K) located in two regions (tetralogy of Fallot and ventricular septal defect) in a Chinese Han population. METHODS: A total of 200 congenital heart disease patients (100 tetralogy of Fallot patients and 100 ventricular septal defect patients) and 100 congenital heart defect-free controls were recruited, and quantitative real-time PCR analysis was used to replicate the association of two copy number variations with congenital heart defects in a Chinese Han population. RESULTS: One deletion at PRKAB2 and one duplication at PPM1K were found in two of the tetralogy of Fallot patients, respectively; while all these regions were duplicated in both ventricular septal defect patients and in the 100 congenital heart defects-free controls. CONCLUSIONS: We replicated the copy number variations at the disease-candidate genes of PRKAB2 and PPM1K with tetralogy of Fallot in a Chinese Han population, and in patients with ventricular septal defect mutations in these two genes were not found. These results indicate the same molecular population genetics exist in these two genes with different ethnicity. This shows that these two genes are possibly specific pf tetralogy of Fallot candidates.

Effects of PPM1K rs1440581 and rs7678928 on serum branched-chain amino acid levels and risk of cardiovascular disease

“…The mechanism is not clear. PPM1K is essential for cell survival and healthy development with the highest expression level in the heart and brain [ 19 ]. As reported in a previous study [ 20 ], reactive oxygen species (ROS) were significantly elevated in the PPM1K-deficient cells, the PPM1K-deficient mitochondria were more susceptible to calcium-induced permeability transition pore opening in the absence of external BCKA/BCAA challenge, and PPM1K as a mitochondrial matrix phosphatase may regulate cardiomyocyte function and viability via modulating ROS and permeability transition pore.…”