GeneID: 48

Description:
This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded protein is expressed in a broad range of cell types, acts as a pleiotropic cytokine and is involved in the stress response program of cells after cellular injury. Protein levels are rapidly enhanced by stress stimuli such as tissue hypoxia, oxidative injury and inflammation. High levels of serum GDF15 associate with ineffective erythropoiesis and may reflect a certain type of bone marrow stress or erythroblast apoptosis. Elevated GDF15 levels are detected in thalassemia (major and intermedia) and sickle cell disease patients. Variants associated with high levels of GDF15 in β-thalassemia have been shown to suppress expression of the iron regulatory protein hepcidin, thereby contributing to iron overload. GDF15 levels were correlated significantly with markers of hemolysis, iron burden, inflammation, endothelial dysfunction and coagulation in HbS/β-thal patients. GDF15 has a multifactorial role in HbS/β-thal disease state, providing utility in identifying a subgroup of higher risk patients.

Synonyms: PLAB , MIC-1 , PDF , MIC1 , NAG-1 , PTGFB

Comments:
N/A

Number of entries/variants: 1

1. Lawton LN, Bonaldo MF, Jelenc PC, Qiu L, Baumes SA, Marcelino RA, de Jesus GM, Wellington S, Knowles JA, Warburton D, Brown S, Soares MB, Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta., Gene , 203(1), 17-26, 1997 PubMed
2. Ago T, Sadoshima J, GDF15, a cardioprotective TGF-beta superfamily protein., Circ. Res., 98(3), 294-7, 2006 PubMed
3. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT, Moroney JW, Reed CH, Luban NL, Wang RH, Eling TE, Childs R, Ganz T, Leitman SF, Fucharoen S, Miller JL, High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin., Nat. Med., 13(9), 1096-101, 2007 PubMed
4. Kempf T, Wollert KC, Growth-differentiation factor-15 in heart failure., Heart Fail Clin , 5(4), 537-47, 2009 PubMed
5. Tanno T, Noel P, Miller JL, Growth differentiation factor 15 in erythroid health and disease., Curr. Opin. Hematol., 17(3), 184-90, 2010 PubMed
6. Athiyarath R, George B, Mathews V, Srivastava A, Edison ES, Association of growth differentiation factor 15 (GDF15) polymorphisms with serum GDF15 and ferritin levels in β-thalassemia., Ann. Hematol. , 93(12), 2093-5, 2014 PubMed
7. Larissi K, Politou M, Margeli A, Poziopoulos C, Flevari P, Terpos E, Papassotiriou I, Voskaridou E, The Growth Differentiation Factor-15 (GDF-15) levels are increased in patients with compound heterozygous sickle cell and beta-thalassemia (HbS/β), correlate with markers of hemolysis, iron burden, coagulation, endothelial dysfunction and pulmonary hypertension., Blood Cells Mol. Dis., 77(0), 137-141, 2019 PubMed