UC San Diego

Background

Genetic variation in calcium signaling pathways is associated with Kawasaki disease (KD) susceptibility and coronary artery aneurysms (CAA). Expression quantitative trait locus analysis for KD-associated variants in calcium/sodium channel gene solute carrier family 8 member 1 (SLC8A1) revealed an effect on expression of urotensin 2 (UTS2). We investigated the role of UTS2 in KD pathogenesis by measuring levels of UTS2 and its receptor in blood and tissues.

Results

UTS2 transcript levels determined by reverse transcription polymerase chain reaction were higher in whole blood of KD subjects homozygous for three risk alleles in SLC8A1 (p=0.002-0.006). Increased levels of plasma UTS2 varied as a function of SLC8A1 genotype (p=0.008-0.04). UTS2 transcript levels in a microarray dataset for 131 subjects remained higher in the convalescent phase of KD in subjects with aneurysms. Immunohistochemical staining identified UTS2 and UTS2R expression in mononuclear inflammatory cells and spindle-shaped cells in the coronary arterial wall of a KD patient with CAA and in a femoral endarterectomy specimen from an adult patient with peripheral aneurysms following KD in childhood.

Discussion

Host genetics influences UTS2 levels, which may contribute to inflammation and cardiovascular damage in KD