BERLIN – A recently identified polymorphism in the fibroblast growth factor 23 gene may be a useful predictor of high risk for coronary artery damage in patients with Kawasaki disease.
Fibroblast growth factor is a phosphorus-regulating hormone. Fibroblast growth factor 23 (FGF23) has previously been identified as a contributor to left ventricular hypertrophy in patients with chronic kidney disease (Circulation 2009;119:2545-52), and as having a possible role in the atherosclerotic process as well. There are FGF23 receptors in the vasculature and in the heart, Dr. Fernanda Falcini explained at the annual European Congress of Rheumatology.
She and her coinvestigators have recently identified an FGF23 polymorphism involving a C insertion in the intronic region between nucleotides 36 and 37. Now they have implicated the polymorphism as having a possible functional role in the predisposition to coronary artery disease in patients with Kawasaki disease.
First the investigators demonstrated that the polymorphism was present in 35% of 100 healthy Italian white subjects. Then they extended their DNA analysis to 118 white patients with Kawasaki disease and 76 age- and sex-matched healthy control children.
The Kawasaki disease patients (median age, 33 months) underwent two-dimensional echocardiography at hospital admission, at day 15, and at 2, 6, and 12 months. Coronary artery damage in the form of an aneurysm or global dilation developed in 28 of the 118 patients.
Of patients with Kawasaki disease, 31% possessed the FGF23 polymorphism. Strikingly, the polymorphism was present in 24 of the 28 patients (86%) with coronary artery disease, but in only 12 of 90 (13%) with normal arteries, reported Dr. Falcini, a rheumatologist at the University of Florence (Italy).
Moreover, Kawasaki disease patients with the FGF23 polymorphism had significantly higher serum FGF23 levels than those with the wildtype FGF23 gene: a mean of 120, compared with 38 pg/mL. How those substantially higher serum levels of the hormone relate to coronary artery damage in patients with Kawasaki disease is a top research priority.
Coronary artery involvement is the most serious and long-lasting complication of Kawasaki disease, and the biggest contributor to the disease’s increased mortality risk. The etiology of the coronary artery damage remains unknown. The leading theory is that an infectious agent elicits a massive systemic inflammatory response directed at cardiovascular tissues. The ability to identify the patient subgroup at high risk for coronary artery damage would enable physicians to develop an aggressive, selectively applied prevention strategy.
The study was funded by an Italian medical research foundation. Dr. Falcini reported having no relevant financial conflicts.