Linkage analysis of five Chinese families with arrhythmogenic right ventricular cardiomyopathy using microsatellite genetic markers

OBJECTIVE: To explore the linkage relationship between specific genetic markers and arrhythmogenic right ventricular cardiomyopathy (ARVC) in Chinese pedigrees. METHODS: The microsatellite genetic markers D2S152, D14S252, and D10S1664 were studied for their linkages to ARVC in five Chinese ARVC pedigrees and a normal population of 121 Chinese individuals. Genomic DNA of the pedigrees and normal population was amplified using PCR techniques. Denaturing polyacrylamide sequencing gel (4%) electrophoresis was used to detect microsatellite repeat polymorphisms. Gels were silver-stained. A classical linkage analysis program was used assuming models of autosomal dominance and recession. RESULTS: The logarithm of the odds (LOD) scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were 2.174, -0.589, -infinity, - (indicating that linkage is not supported in this mode), and -infinity respectively in autosomal dominant model (recombination fraction = 0.000 respectively)and were -infinity, -infinity, -infinity, -infinity, and 0.182 respectively in the autosomal recessive model. The LOD scores of D14S252 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -, -infinity, -, and 0 respectively in autosomal dominant model, and were -infinity, -0.812, -infinity, -infinity, and 0.087 respectively in autosomal recessive model. The LOD scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -0.539, -, and 0.602 respectively in autosomal dominant model and were -, -infinity, -infinity, -infinity, and - infinity respectively in autosomal recessive model. CONCLUSIONS: The LOD score for D2S152 in the LW pedigree was 2.174, indicating that the chance of linkage is about 150:1. This suggests that there is a possible ARVC-related gene near this marker. There were no clear linkage relationships between ARVC and D10S1664 and D14S252 in this family, and no linkages between ARVC and any of the three genetic markers in the other four families. These results also suggest that there is genetic heterogeneity in LW and in the other pedigrees.