OP0276 Fibroblast growth factor (FGF23) gene polymorphism in kawasaki disease: A risk of coronary damage
Authors: F. Falcini, L. Masi, F. Franceschelli, G. Leoncini, S. Ciuffi, D. Rigante, F. La Torre, M. Matucci Cerinic, M.L. Brandi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Kawasaki disease may be complicated by coronary artery disease (CAD): genetic predisposition might play a role in the susceptibility both to KD and CAD. FGF23, a novel phosphaturic factor that influences phosphate renal reabsorption acts through FGF-receptor1 on the vasculature and heart. A study of our group (submitted work) has detected high serum FGF23 levels in all patienta with KD mainly in those with coronary artery involvement. <h3>Objectives</h3> To investigate <i>FGF23</i> gene looking for possible mutations or polymorphisms responsible of abnormal serum FGF23 levels and evaluate a potential predisposition to CAD. <h3>Methods</h3> Genomic DNA extracted from peripheral blood and the 3 <i>FGF23</i> exons, including the intron-exon boundary regions, were PCR-amplified and analyzed on ABI Prism 3100 genetic analyzer (Applied Biosystems, Foster City, CA). The obtained sequences were compared to the wild type reference sequence of the <i>FGF23</i> gene published on Genbank Database (NT-009759).Intact FGF23 was measured using an ELISA method (Immunotopics Inc. San Clemente, CA, USA). One hundred and eighteen KD Caucasian pts, 75M, 43F, median age 32.5 months were studied. Twenty eight out of 118 developed CAD. All underwent 2D-echocardiogram at admission, 15 days, 2, 6, 12 months. Pts with CAD were more closely controlled. Seventy-six sex-age-matched healthy children were used as controls, after clinical and laboratory exclusion of rheumatic, endocrinological and chronic renal diseases. Ethical Committee's approval and informed consents by relatives were obtained. Pearson's chi-square (χ<sup>2</sup>) analysis was performed to evaluate the distribution of <i>FGF23</i> gene polymorphisms in the population. Analysis of covariance (ANCOVA), followed by LSD protected least significant difference, was performed to evaluate the correlation between <i>FGF23</i> polymorphisms and serum FGF23 values. Results were expressed as means ±SEM. <h3>Results</h3> DNA analysis has shown a new C insertion in the intronic region between -36 and -37 nucleotide (rs3832879:NM_020638.2:c.212-37_212-36insC). Subjects without <i>FGF23</i> polymorphism were indicated as WT, homozygous as pattern1 and heterozygous as pattern 2. To verify the frequency of the rs3832879 variant and evaluate the presence of polymorphic changes, DNA analysis of 100 Caucasian voluntaries confirmed this change. The χ<sup>2</sup> analysis showed that 36.5% of the total population carried out the polymorphic site, and 63.5% not. Only 13.56% of KD pts without CAD had the <i>FGF23</i> polymorphism, while it was present in 85.19% of pts with CAD (χ<sup>2</sup>: 41.2; df=1, <i>p</i>=0.001). ANCOVA analysis showed a statistically significant correlation between the presence of polymorphism and serum FGF23 levels. Pts WT had lower levels of serum FGF23 than heterozygotes and homozygotes (54.4±23 SD <i>vs</i> 51,9±28 and 135,3±35). All pts with <i>FGF23</i> polymorphysm had higher FGF23 serum levels than those without (120±40 <i>vs</i> 38.2±5). <h3>Conclusions</h3> From our preliminary data the segregation of <i>FGF23</i> genotype with the CD advocates a possible functional role of this new polymorphism in the predisposition to CAD in pts with KD. <h3>Disclosure of Interest</h3> None Declared