Investigation of OPG/RANK/RANKL Genes as a Genetic Marker for Cardiac abnormalities in Thalassemia Major Patients

Objective The aim of the study was to investigate the role of osteoprotegerin (OPG)/RANK/RANKL variants in left ventricular hypertrophy (LVH) and diastolic dysfunction in thalassemia major patients Materials and Method One hundred and five beta-thalassemia patients who were older than 10 years of age were enrolled for the study. Two-dimensional and M-mode echocardiography analysis was done in all patients. Genotyping for OPG [rs2073617 (950 T>C), rs2073618 (1181G>C)], RANK [(rs1805034(+34694 C>T), rs12458117 (+34901 G>A) and rs75404003 (+35966insdelC)], and RANKL (rs2277438, rs9594782) variants was done using the PCR-RFLP method. Serum OPG levels were estimated by ELISA. Results Mean age of patients was 16.36 +/- 5.08 years. LVH and diastolic dysfunction was present in 33 (31.4%) and 24 (22.8%) patients, respectively. Thalassemia patients having minor allele of OPG rs2073618, RANK rs75404003 and RANKL rs9594782 SNPs were at high risk for LVH as suggested by high odds ratio of 2.470, 3.783, and 2.148, respectively; however, none of the SNPs tested were statistically significantly associated after applying Bonferroni corrections for multiple testing adjustment. No significant association of any SNP with diastolic dysfunction was observed. Serum OPG levels were found significantly higher in thalassemia patients with diastolic dysfunction (P = 0.006). Conclusion OPG rs2073618, RANK rs75404003, and RANKL rs9594782 SNPs may predispose LVH in thalassemia patients. Patients with diastolic dysfunction showed increased levels of serum OPG.