title: 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>5 mm) (case: n=17). Twelve loci with one or more sequence variants were found to be significantly associated with CALs (P<1 × 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>5 mm) and 191 KD patients without CALs (odds ratio (OR)=12.6, P(combined)=1.96 × 10(-8)). This result indicates that the KCNN2 gene can have an important role in the development of coronary artery aneurysms in KD.
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jae-Jung
authors.initials: JJ
authors.lastname: Kim
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Park
authors.forename: Dankyu
authors.initials: D
authors.lastname: Yoon
authors.forename: Kyung-Yil
authors.initials: KY
authors.lastname: Lee
authors.forename: Min
authors.initials: M
authors.lastname: Seob Song
authors.forename: Hyoung
authors.initials: H
authors.lastname: Doo Lee
authors.forename: Kwi-Joo
authors.initials: KJ
authors.lastname: Kim
authors.forename: In-Sook
authors.initials: IS
authors.lastname: Park
authors.forename: Hyo-Kyoung
authors.initials: HK
authors.lastname: Nam
authors.forename: Sin
authors.initials: S
authors.lastname: Weon Yun
authors.forename: Myung
authors.initials: M
authors.lastname: Ki Han
authors.forename: Young
authors.initials: Y
authors.lastname: Mi Hong
authors.forename: Gi
authors.initials: G
authors.lastname: Young Jang
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
mesh_terms: D002675:Child, Preschool; D003323:Coronary Aneurysm / Q000150:complications* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D015203:Reproducibility of Results; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*
chemical_list: C496897:KCNN2 protein, human; D051640:Small-Conductance Calcium-Activated Potassium Channels