Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


A New Polymorphism of the Fibroblast Growth Factor (FGF) 23 Gene: A Promising Predictor of Coronary Damage in Kawasaki Disease (KD).

Falcini1,  Fernanda, Masi3,  Laura, Franceschelli3,  Francesco, Leoncini3,  Gigliola, Capannini1,  Serena, La Torre4,  Francesco, Calcagno4,  Giuseppina

Department of BioMedicine, Section of Rheumatology, Transition Clinic, University of Florence, Florence, Italy
Department of BioMedicine, Section of Rheumatology, Transition Clinic, University of Florence, Florence, Italy
Department of Internal Medicine, Metabolic Bone Diseases Unit, University of Florence, Italy
Department of Paediatrics, Rheumatology Unit, University of Messina

Background:

Vascular endothelial cell damage is crucial in KD, acute systemic vasculitis complicated by arterial dysfunction. Intimal thickening and fibrosis are reported in KD coronary arteries. Several pts even timely treated with IVIG may develop coronary artery abnormalities (CAA) with risk of ischemic heart disease. Phosphatonins are new hormones involved in phosphate homeostasis and bone mineralization. FGF23, the master phosphatonin, acts through FGFr1 present in vasculature and heart. Fgf23 knockout mice develop ectopic calcifications and vascular and heart damage assuming that FGF23 contribute to the development of vascular injury.

Aims:

1.To measure the intact FGF23 serum levels in KD pts. 2.To assess the association between FGF23 levels and CAA 3.To screen KD pts for FGF23 gene mutation looking at a possible role of FGF23 allelic variants in cardiac damage.

Patients:

95 KD pts (58 M,37F, median age 30.5 mths) after informed consent entered the study. 30 age-sex matched healthy children acted as controls All pts had received IVIG and ASA. In all, at baseline and at study entry lipid profile (cholesterol, HDL, LDL, tryglicerides) was evaluated.

Methods:

Serum intact FGF23 level was measured, using an ELISA assay (Immunotopics Inc. San Clemente, CA, USA).Genomic DNA was extracted from peripheral blood and the 3 FGF23 exons, including the intron-exon boundary regions, were PCR-amplified and analyzed on ABI Prism 3100 Genetic Analyzer (Applied Biosystems, Foster City, CA.

Results:

KD pts have higher FGF23 serum levels than controls (72+/-40SD vs 12,3+/-3.2SD pg/ml. Student's T Test: p=0.01).DNA analysis shows a new C insertion in the intronic region between -36 and -37 nucleotide close to the exon 2 (rs3832879: NM_020638.2:c.212-37_212-36insC).All pts (18M,10F) with polymorphic allelic variant have CAA (aneurysms, dilatations), and display higher levels of serum FGF23 than pts without polymorphic site (120+/- 40 vs. 38.2+/- 5).

Conclusions:

From our preliminary data the segregation of FGF23 genotype with the CAA advocates a possible functional role of the new polymorphism in KD coronary artery injury. These data point to FGF23 gene polymorphism and serum FGF23 levels as two potential predictors of high risk of CAA. So far, no individual genotype data are available for FGF23 gene polymorphism.

To cite this abstract, please use the following information:
Falcini, Fernanda, Masi, Laura, Franceschelli, Francesco, Leoncini, Gigliola, Capannini, Serena, La Torre, Francesco, et al; A New Polymorphism of the Fibroblast Growth Factor (FGF) 23 Gene: A Promising Predictor of Coronary Damage in Kawasaki Disease (KD). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2202
DOI: 10.1002/art.29966

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