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OP0276 Fibroblast growth factor (FGF23) gene polymorphism in kawasaki disease: A risk of coronary damage
  1. F. Falcini1,
  2. L. Masi2,
  3. F. Franceschelli2,
  4. G. Leoncini2,
  5. S. Ciuffi2,
  6. D. Rigante3,
  7. F. La Torre4,
  8. M. Matucci Cerinic5,
  9. M.L. Brandi2
  1. 1Internal Medicine, Rheumatology Section, Transition Clinic
  2. 2Internal Medicine, Endocrinology Unit, University of Florence, Firenze
  3. 3Pediatrics Sciences, Università Cattolica Sacro Cuore, Roma
  4. 4DIMIMP Rheumatology, University of Bari, Bari
  5. 5Internal Medicine Rheumatology Section, University of Florence, Firenze, Italy

Abstract

Background 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.

Objectives To investigate FGF23 gene looking for possible mutations or polymorphisms responsible of abnormal serum FGF23 levels and evaluate a potential predisposition to CAD.

Methods Genomic DNA 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). The obtained sequences were compared to the wild type reference sequence of the FGF23 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 (χ2) analysis was performed to evaluate the distribution of FGF23 gene polymorphisms in the population. Analysis of covariance (ANCOVA), followed by LSD protected least significant difference, was performed to evaluate the correlation between FGF23 polymorphisms and serum FGF23 values. Results were expressed as means ±SEM.

Results 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 FGF23 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 χ2 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 FGF23 polymorphism, while it was present in 85.19% of pts with CAD (χ2: 41.2; df=1, p=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 vs 51,9±28 and 135,3±35). All pts with FGF23 polymorphysm had higher FGF23 serum levels than those without (120±40 vs 38.2±5).

Conclusions From our preliminary data the segregation of FGF23 genotype with the CD advocates a possible functional role of this new polymorphism in the predisposition to CAD in pts with KD.

Disclosure of Interest None Declared

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