ABSTRACT
Gene expression level of 2900 genes was studied by cDNA microarray in patients with atrial fibril-lation (AF) or sinus rhythm. Gene transcripts were analysed in samples of right atrial appendages from 47 patients undergoing surgery for valve repair or coronary artery bypass. Standard correlation analysis and two dimensional hierarchical clustering were used for study of differentially expressed genes in patient groups. A highly positive correlation of gene expression with AF was shown for cardiac muscle LIM domain protein (CSRP3), cardiac muscle myosin heavy chain beta isoform (MYH7), calmodulin (CALMS) and homeobox protein (PKNOXl) genes (r > 0.77, p < 0.007). In contrast, metallothionein (MT1/2), mitochondrial aldehyde dehydrogenase 2 (ALDH2), ras-related protein (RaplA) and guanine nucleotide binding protein G (GNAL) genes revealed highly negative correlation with AF (r < -0.75, p < 0.002). Alterations of gene activity were more evident at permanent as compared with paroxysmal AF. In addition, genes overexpressed in AF patients demonstrated underexpression in coronary artery disease patients (r=-0.8, p=0.0002) and conversely. Genes correlating with AF belong to different functional categories, including sarcomere organization, contraction, Ca2+ homeostasis, signaling and transcription regulation, extracellular matrix interactions and oxidative stress. Downregulation of MT1/2 and ALDH2 genes, known protectors against oxidative stress, may contribute to maintenance of oxidative stress in myocardial tissues of AF patients. The identification of novel genes - participants of pathological process in AF may open new perspective for search of therapeutic agents.
Subject(s)
Atrial Appendage/metabolism , Atrial Fibrillation/genetics , DNA, Complementary/genetics , Gene Expression , Muscle Proteins/genetics , Myocytes, Cardiac/metabolism , Oligonucleotide Array Sequence Analysis/methods , Adult , Aged , Atrial Appendage/pathology , Atrial Fibrillation/metabolism , Atrial Fibrillation/pathology , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Muscle Proteins/biosynthesis , Myocytes, Cardiac/pathology , Reproducibility of ResultsABSTRACT
A data retrieval system CHRODYS combines databases on autosomal human dysmorphism. This system is based on the reported case descriptions of patients from our practice in 1970s-1990s. The system CHRODYS differs from similar systems by strict selection of data on partial and complete autosomal trisomies and monosomies for cytogenetic parameters. This is necessary for revealing syndromes of congenital malformations of chromosomal origin. As a collection of genetic data, the system may serve as a useful reference for solving both theoretical and applied tasks in human genetics. One of the blocks of this system concerning cytogenetic mapping of pathologic phenotypes, caused by aberrations of human chromosome 2, is presented in detail.
