UC San Diego

BackgroundGenetic 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 speculated that UTS2 is influenced by genetic variation in SLC8A1 and contributes to disease pathogenesis.MethodsWe measured levels of UTS2 and its receptor in blood and tissues using quantitative reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining.ResultsUTS2 transcript levels were higher in the whole blood of subjects with KD 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 and UTS2 receptor were expressed in mononuclear inflammatory cells and spindle-shaped cells in the coronary arterial wall of a patient suffering from KD with CAA and in a femoral endarterectomy specimen from an adult patient with peripheral aneurysms following KD in childhood.ConclusionHost genetics influences UTS2 levels, which may contribute to inflammation and cardiovascular damage in KD.