Genetic variations of β-MYH7 in hypertrophic cardiomyopathy and dilated cardiomyopathy.

CONTEXT: Hypertrophic cardiomyopathy (HCM) is known to be manifested by mutations in 12 sarcomeric genes and dilated cardiomyopathy (DCM) is known to manifest due to cytoskeletal mutations. Studies have revealed that sarcomeric mutations can also lead to DCM. Therefore, in the present study, we have made an attempt to compare and analyze the genetic variations of beta-myosin heavy chain gene (β-MYH7), which are interestingly found to be common in both HCM and DCM. The underlying pathophysiological mechanism leading to two different phenotypes has been discussed in this study. Till date, about 186 and 73 different mutations have been reported in HCM and DCM, respectively, with respect to this gene. AIM: The screening of β-MYH7 gene in both HCM and DCM has revealed some common genetic variations. The aim of the present study is to understand the pathophysiological mechanism underlying the manifestation of two different phenotypes. MATERIALS AND METHODS: 100 controls, 95 HCM and 97 DCM samples were collected. Genomic DNA was extracted following rapid nonenzymatic method as described by Lahiri and Nurnberger (1991), and the extracted DNA was later subjected to polymerase chain reaction (PCR) based single stranded conformation polymorphism (SSCP) analysis to identify single nucleotide polymorphism (SNP)s/mutations associated with the diseased phenotypes. RESULTS AND CONCLUSION: Similar variations were observed in β-MYH7 exons 7, 12, 19 and 20 in both HCM and DCM. This could be attributed to impaired energy compromise, or to dose effect of the mutant protein, or to even environmental factors/modifier gene effects wherein an HCM could progress to a DCM phenotype affecting both right and left ventricles, leading to heart failure.

Epidemiology and genetics of dilated cardiomyopathy in the Indian context.

Background: Dilated cardiomyopathy (DCM) still remains to be a poorly understood and less analyzed group of cardiac-muscle disorders when compared to hypertrophic cardiomyopathy (HCM). Also, the vast clinical heterogeneity among the patients has rendered the small and isolated kindred studies less informative on the genetics and epidemiology of DCM. Aim of the study: The study aimed at understanding the epidemiology and genetics of DCMs in the Indian context. Materials and methods/ Statistical analysis: One hundred seven DCM patients and 105 healthy individuals were included in the study for epidemiological and genetic risk factor identification and to fit the possible mode of inheritance. Single's ascertainment methodology for segregation analysis and Penrose frequency estimates were followed to evaluate for the role of specific epidemiological factors in the disease etiology. Chi-square analysis was carried out to interpret the results statistically. Results and Conclusion: Our study suggests that epidemiological factors like gender, age at onset and vegetarian diet in conjunction with sarcomere gene mutations may play a role in the disease expression. Similarly, segregation analysis for the possible mode of inheritance showed a deviation from the autosomal dominant mode of inheritance, strengthening the underlying genetic heterogeneity of DCM.

Linkage analysis of three families with arrythmogenic right ventricular cardiomyopathy in India.

BACKGROUND: Arrythmogenic Right Ventricular Cardiomyopathy (ARVC) is a primary myocardial disorder morphologically characterized by subtle to severe replacement of the right ventricular myocardium by fatty and fibrous tissue. ARVC is known to be highly prevalent in European population with recent reports implicating it to be a major cause of sudden death in young individuals even from American and Asian population. AIM: To implicate or exclude TMEM43 (ARVC-5), DSP(ARVC-8) genes and the yet to be identified gene at ARVC-6 locus in the pathogenesis in three families affected with ARVC from India. MATERIALS AND METHODS: Three families comprising of 42 affected/unaffected members were included in the study. Three microsatellite markers, D3S3613 (ARVC5) D10S1664 (ARVC6), D6S309 (ARVC8) were genotyped by PCR-based native PAGE. Two-point Linkage analysis was performed using LINKAGE program version 5.2 RESULTS AND DISCUSSION: LOD scores from linkage analysis for the microsatellite marker D10S1664 (ARVC-6) in families KS and REV have shown positive value hinting the involvement of this locus in the etiology of ARVC, while linkage analysis in the SB family ruled out involvement of DSP, TMEM43 and ARVC-6, as negative LOD scores were obtained with all three loci. Therefore, linkage analysis carried out in the present study indicates that ARVC-6 (cumulative LOD score is equal to plus 1.203376 at θ is equal to 0.05) could be the locus harboring the mutated gene in two out of three families.