No abstract

Despite considerable public awareness and technological advances that foster early diagnosis and aggressive therapeutic interventions, heart failure, which results as a final outcome from an underlying cardiovascular disorder remains a critical and an unsolved problem. Among the various cardiomyopathies, Dilated cardiomyopathy with an obscure etiology is known to be the leading cause of heart failure and sudden cardiac death among young adults and children. Studies related to the molecular basis of the condition have implicated oxidative stress pathways, apart from primary disease causing sarcomeric, cytoskeletal and mitochondrial gene mutations in the disease onset. The present study aims to evaluate the role of oxidative stress markers in 97 DCM patients and 105 control individuals to identify specific electromorphic association of superoxide dismutase, catalase and alpha-1-antitrypsin with the disease. Our study has revealed an association of SODA2, catalase HPII and AAT 'M' and 'Z' alleles with DCM, thereby resulting in inefficient scavenging of the free radicals, which may confer decreased protection against oxidative stress induced tissue injury in the disease pathogenesis. The involvement of SOD and AAT in apoptotic pathway and as immunomodulators is also emphasized.

Cardiomyopathies are a heterogeneous group of heart muscle disorders responsible for a great deal of morbidity and mortality. Dilated, hypertrophic and restrictive are the three major categories of cardiomyopathies. Since reactive oxygen species has been implicated in wide range of genetic disorders and the role of antioxidant like superoxide dismutase as a scavenger has been highlighted, the present study envisages on identifying the specific electromorphic association of superoxide dismutase with cardiomyopathies and to delineate the genetic heterogeneity based on specific alleles at risk. Phenotyping was carried out on 8% PAGE of the red cell membrane samples following Davies (1964) and Beauchamp's (1975) protocols. Blood samples from 62 dilated cardiomyopathy, 80 hypertrophic cardiomyopathy and 86 healthy individuals were collected from CARE Hospitals and voluntary blood donor camps, Hyderabad. Significant association of homozygous SOD A*1 (χ 2 = 7.58) alleles with dilated cardiomyopathy and heterozygous SOD A*2-1 (χ 2 = 5.89) alleles with hypertrophic cardiomyopathy was observed, resulting in significant deviation of allelic frequency in cardiomyopathy group compared to the control group highlighting that individuals carrying SOD A*1 (χ 2 = 7.588) and SOD A*2-1 (χ 2 = 5.89) alleles may be at a greater risk for dilated and hypertrophic cardiomyopathy respectively. Thus SOD as a genetic marker may help in risk prediction and in delineating genetic heterogeneity of the condition and the role of superoxide dismutase with specific electromorphic association in influencing endogenous nitric oxide production and energy pathways by altering the structure and function of the cell membranes is discussed.