title: Investigation of OPG/RANK/RANKL Genes as a Genetic Marker for Cardiac abnormalities in Thalassemia Major Patients.
abstract: 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).
  
  
  CONCLUSIONS
  OPG rs2073618, RANK rs75404003, and RANKL rs9594782 SNPs may predispose LVH in thalassemia patients. Patients with diastolic dysfunction showed increased levels of serum OPG.
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Mable Misha
authors.initials: MM
authors.lastname: Singh
authors.affiliation: Central Research Laboratory, Sri Aurobindo Medical College and Post Graduate Institute Indore, Madhya Pradesh, India.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Cardiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Satyendra
authors.initials: S
authors.lastname: Tewari
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Sarita
authors.initials: S
authors.lastname: Agarwal
mesh_terms: D000293:Adolescent; D003971:Diastole / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics; D016015:Logistic Models; D008297:Male; D053244:Osteoprotegerin / Q000235:genetics*; D053245:RANK Ligand / Q000235:genetics*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics*; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human
keywords: Beta-thalassemia major; Echocardiography; OPG; RANK; RANKL; SNP