Studying the Genetics involved causing cardiac damage in Thalassemia major Patients A cause of morbidity and mortality

Abstract

Beta Thalassemia major (and#946;-TM) is an autosomal recessive disorder of the newlineblood, caused by mutationsin the beta globin gene. The condition leads to reduced or newlineno haemoglobin causing ineffective erythropoiesis resulting in anemia. Chronic newlinetransfusions,to cope with anemia, leads to abnormally high levels of serum ferritin newlineresulting in iron overload. Cardiac complications are a major cause of morbidity and newlineaccounts for 71% of the total mortality in Beta Thalassemia patients. newlineChronic iron deposition in the cardiomyocytes leads to cardiac newlineremodelling affecting the structure which then eventually affects the functioning of newlinethe heart. Genetic variation contributes for the remodelling and also may pre-dispose newlinepatients to cardiovascular complications. Diastolic dysfunction is the most common newlinecardiovascular problem in and#946;-TM patients which may occur due to structural changes newlinelike left ventricular hypertrophy, vascular damage and oxidative damage due to newlinegeneration of free radicals. newlineOPG/RANK/RANKL pathway has been implicated in immunoinflammatory cardiovascular problems. A similar condition is also observed in and#946;-TM newlinepatients due iron overload. In Present study group left ventricular hypertrophy (LVH) newlinewas present in 31.4% and diastolic dysfunction was present in 22.8%. NT-proBNP is newlinethe chemical released in wall stress due to deposition of iron in the myocardium. newlineAssessing NT-proBNP in the samples lead to the significant association in patients newlinewith diastolic dysfunction (plt0.001). E/E ratio (r=0.664, plt0.001) and E/A newlineratio(r=0.614, plt0.001) and positively correlated with serum NT-proBNP. newline Genetics variants of OPG, RANK and RANKL studied were found to newlinesignificantly contribute for LVH which would progress to diastolic dysfunction. newlineThalassemia patients having minor allele of OPG rs2073618, RANK rs75404003 and newlineRANKL rs9594782 SNPs were at high risk for LVH as suggested by high odds ratio newlineof 2.470, 3.783, and 2.148, respectively. Serum OPG levels were found to be newlinesignificantly higher in Thalassemia patients with diastolic dysfunction