The Population Prevalence And Single Nucleotide Polymorphism Of Desmosomal Mutations Predisposing To Arrhythmogenic Right Ventricular Cardiomyopathy In Chinese Han

Objective This study examined the population prevalence and single nucleotide polymorphism (SNP) of desmosomal mutations predisposing to Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) in Chinese Han.Methods A total of 50 subjects were recruited into this study based on the Original International Task Force Criteria of ARVC. Clinical data were reassessed according to Modified Criteria for Diagnosis of ARVC. For each variant,198 unrelated healthy individuals were compared with the study subjects. Venous blood was obtained and DNA was extracted. DNA sequence of all 5 desmosome genes (PKP2, DSP, DSG2, DSC2, JUP) was analyzed. Polymerase chain reaction (PCR) and direct sequencing were used to be screened all exons of desmosome genes. Find SNPS and mutations in desmosomal proteins related to ARVC.Mutation types were determined via bioinformation analysis, and their possible impact on protein function was estimated.Results Among all the subjects studied,37 of them were diagnosed with ARVC,9 with a borderline diagnosis, and 4 with a possible diagnosis. Distribution of gene mutations was 27%(10 of 37) for PKP2,14% for DSP (5 of 37),11%(4 of 37) for DSG2,5% for JUP (2 of 37), and 3% for DSC2 (1 of 37).37 different mutations were identified in 33 (16.7%) healthy individuals.34 mutations were novel, and 3 have been reported. Distribution of gene mutations was 2%(4 of 198) for PKP2,8.6% for DSP (17 of 198),4%(8 of 198) for DSG2,2% for JUP (4 of 198), and 4% for DSC2 (2 of 198). Fisher’s exact test showed that the distribution of PKP2 mutation in ARVC subjects was significantly different when compared with healthy controls (P<0.00\). In this study,18 SNPs with changed amino acid were found in ARVC subjects, including 9 SNPs in DSP,2 SNPs in PKP2, JUP, and DSC2 respectively,and 3 SNPs in DSG2.2 SNPs in JUP and DSC2 gene (D71D and I776I) were associated with the occurrence of ARVC, while other alleles frequencies were comparable between the patients and the controls.Conclusions 42 of 198 Chinese Han carry a desmosomal mutation.2 SNPs of JUP and DSC2 gene (D71D and I776I) were associated with ARVC. Other SNPs were no associated with ARVC, suggesting further research should be performed to clarify the role of desmosomal mutations in the occurrence of ARVC.