Identification of KCNN2 as a susceptibility locus for coronary artery aneurysms in Kawasaki disease using genome-wide association analysis

Abstract

Kawasaki disease (KD) is often complicated by coronary artery lesions (CALs), including aneurysms. Because of the complications associated with KD, this disorder is the leading cause of acquired heart disease in children from developed countries. To identify genetic loci that confer a higher risk of developing CALs, we performed a case-control association study using previous genome-wide association study data for samples from KD cases only (n = 186) by grouping KD patients without CALs (control: n = 123) vs KD patients with extremely large aneurysms (diameter>5mm) (case: n 17). Twelve loci with one or more sequence variants were found to be significantly associated with CALs (P<1 x 10(-5)). Of these, an SNP (rs17136627) in the potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 (KCNN2) at 5q22.3 was validated in 32 KD patients with large aneurysms (diameter>5mm) and 191 KD patients without CALs (odds ratio (OR) 12.6, P-combined = 1.96 x 10(-8)). This result indicates that the KCNN2 gene can have an important role in the development of coronary artery aneurysms in KD.