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Published on: March 14, 2017
OPG/RANK/RANKL axis relation to cardiac iron-overload in children with transfusion-dependent thalassemia
Samira Zein Sayed1, Asmaa Hosni Abd El-Hafez1, Mostafa Ahmed Abu El-Ela2
1Department of Pediatrics, Faculty of Medicine, Minia University, El Minya, Egypt.
Insights
Genetic variations in the OPG/RANK/RANKL axis may serve as biomarkers for iron-overload cardiomyopathy in children with transfusion-dependent thalassemia (TDT). Specific polymorphisms were linked to myocardial iron levels and cardiac function in TDT patients.
Area of Science:
- Genetics
- Cardiology
- Hematology
Background:
- The OPG/RANK/RANKL axis is implicated in various diseases, including bone and cardiovascular conditions.
- Iron-overload cardiomyopathy is a significant complication in children with transfusion-dependent thalassemia (TDT).
Purpose of the Study:
- To investigate the association between OPG, RANK, and RANKL gene polymorphisms and alleles and the development of iron-overload cardiomyopathy in TDT children.
- To assess the relationship between these genetic variations and myocardial iron status and cardiac function.
Main Methods:
- Genotyping of OPG (rs207318), RANK (rs1805034, rs1245811, rs75404003), and RANKL (rs9594782, rs2277438) polymorphisms using real-time PCR in 80 TDT children and 80 controls.
- Cardiac assessment using T2* MRI for myocardial iron load and ejection fraction (EF) for cardiac function.
Main Results:
- No significant differences in polymorphism frequencies were observed between TDT cases and controls.
- OPG rs2073618 (G>C) polymorphism was associated with myocardial iron overload (p=0.02), with the C allele linked to better EF (p=0.04).
- RANK rs75404403 (C>DEL) was related to cardiac dysfunction (p=0.02), with the C allele showing more frequent affected EF (p=0.02).
- RANKL rs2277438 (G>A) showed the A allele was associated with less frequent severe cardiac iron overload (p=0.04).
Conclusions:
- The OPG/RANK/RANKL gene pathway may function as genetic markers for iron-induced cardiomyopathy in TDT.
- Specific polymorphisms and alleles within these genes are significantly associated with myocardial iron overload and cardiac dysfunction in TDT children, highlighting their potential as predictive markers.
Abstract:
OPG/RANK/RANKL axis was reportedly involved in initiating various diseases, especially bone and cardiovascular diseases. This study aimed to assess the relationship between some OPG, RANK, and RANKL polymorphisms and alleles and iron-overload-induced cardiomyopathy in children with transfusion-dependent thalassemia (TDT). This study included 80 TDT children and 80 age and sex-matched controls. Real-time PCR was done for rs207318 polymorphism for the OPG gene and rs1805034, rs1245811, and rs75404003 polymorphisms for the RANK gene, and rs9594782 and rs2277438 polymorphisms for the RANKL gene. Cardiac T2* MRI and ejection fraction (EF) were done to assess the myocardial iron status and cardiac function. In this study, there were no significant differences in frequencies of the studied polymorphisms between cases and controls (p > 0.05 in all). In TDT children, OPG rs2073618 (G > C) had a significant relation to myocardial iron overload (p = 0.02). Its C allele had significantly more frequent normal EF than its G allele (p = 0.04). RANK rs75404403 (C > DEL) had a significant relation to cardiac dysfunction (p = 0.02). Moreover, the C allele of that gene had significantly more frequent affected EF than its DEL allele (p = 0.02). The A allele of RANKL rs2277438 (G > A) had significantly less frequent severe cardiac iron overload than the G allele (p = 0.04). In conclusion, the OPG/ RANK/RANKL genes may act as genetic markers for iron-induced cardiomyopathy in TDT children. Some of the studied genes' polymorphisms and alleles were significantly related to myocardial iron overload and cardiac dysfunction in TDT children.
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