OBJECTIVE: To explore the correlation between DSG2, TTN and GATA4 genes and Brugada syndrome in Henan Province of China. METHODS: From February 2017 to February 2019, 100 patients with Brugada syndrome and 100 healthy individuals were selected as the study and the control groups, respectively. Electrocardiogram and echocardiography were carried out, and peripheral blood samples was collected. Coding regions of DSG2, TTN and GATA4 genes were amplified by PCR and sequenced. The results were compared with standard sequences from GenBank. RESULTS: Electrocardiogram showed that all patients from the study group had ventricular arrhythmia, 87 cases (87%) presented ventricular tachycardia (VT), 84 cases (84%) presented T wave inversion, and 51 cases (51%) presented Epsilon wave. Echocardiography showed that the right ventricle in the study group was enlarged with the inner diameter of the right ventricle being (40.0±13.3) mm, and the right ventricle showed various degree of abnormal systolic function. The enlargement of right atrium accounted for 64%, and the involvement of the left ventricle accounted for 27%. The right ventricular diameter and left ventricular diastolic diameter of the study group were significantly greater than those of the control group (P< 0.05). DNA sequencing showed that 60 patients carried DSG2 gene variants, among which 18 had missense variant of exon 8. Fifty patients carried TTN gene variants, including 8 in the A-band domain and 3 in the I-band domain. Twenty patients carried 3 variants of the GATA4 gene. CONCLUSION Variants of the DSG2, TTN and GATA4 genes in Henan region are correlated with the onset of Brugada syndrome.
Arrhythmogenic Right Ventricular Dysplasia ; Brugada Syndrome/genetics* ; China ; Connectin ; Desmoglein 2/genetics* ; GATA4 Transcription Factor ; Humans ; Pedigree ; Sequence Analysis, DNA

OBJECTIVE: To investigate the effect of silencing CD46 and desmoglein 2 (DSG2) in host A549 cells on the entry of human adenovirus type 3 (HAdV-3) and type 7 (HAdV-7) and host cell secretion of inflammatory cytokines. METHODS: RNA interference technique was use to silence the expression of CD46 or DSG2 in human epithelial alveolar A549 cells as the host cells of HAdV-3 or HAdV-7. The binding of the viruses with CD46 and DSG2 were observed with immunofluorescence staining at 0.5 and 1 h after viral infection. The viral load in the host cells was determined with qRT-PCR, and IL-8 secretion level was measured using ELISA. RESULTS: In infected A549 cells, immunofluorescent staining revealed colocalization of HAdV-3 and HAdV-37 with their receptors CD46 and DSG2 at 0.5 h and 2 h after infection, and the copy number of the viruses increased progressively after the infection in a time-dependent manner. In A549 cells with CD46 silencing, the virus titers were significantly lower at 2, 6, 12 and 24 h postinfection in comparison with the cells without gene silencing; the virus titers were also significantly decreased in the cells with DSG2 silencing. The secretion level of IL-8 increased significantly in A549 cells without siRNA transfection following infection with HAdV-3 and HAdV-7 (P < 0.0001), but decreased significantly in cells with CD46 and DSG2 silencing (P < 0.0001). CONCLUSION HAdV-3 and HAdV-7 enter host cells by binding to their receptors CD46 and DSG2, and virus titer and cytokines release increase with infection time. Silencing CD46 and DSG2 can inhibit virus entry and cytokine IL-8 production in host cells.
A549 Cells ; Adenoviruses, Human/metabolism* ; Desmoglein 2/metabolism* ; Humans ; Interleukin-8 ; Membrane Cofactor Protein/genetics* ; RNA, Small Interfering

BACKGROUNDArrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes.

METHODSA total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C.

RESULTSFifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in non-desmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them (one of each gene) appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers.

CONCLUSIONSPlakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Non-desmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.

Adult ; Arrhythmogenic Right Ventricular Dysplasia ; genetics ; metabolism ; Asian Continental Ancestry Group ; Desmin ; genetics ; Desmoglein 2 ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Plakophilins ; genetics ; Young Adult ; gamma Catenin ; genetics