title: Common variants in the CRP promoter are associated with a high C-reactive protein level in Kawasaki disease.
abstract: Kawasaki disease (KD) is an acute self-limiting form of vasculitis that afflicts infants and children and manifests as fever and signs of mucocutaneous inflammation. Children with KD show various laboratory inflammatory abnormalities, such as elevations in their white blood cell (WBC) count, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). We here performed a genome-wide association study (GWAS) of 178 KD patients to identify the genetic loci that influence 10 important KD laboratory markers: WBC count, neutrophil count, platelet count, CRP, ESR, hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and total protein. A total of 165 loci passed our arbitrary stage 1 threshold for replication (p < 1 × 10(-5)). Of these, only 2 SNPs (rs12068753 and rs4786091) demonstrated a significant association with the CRP level in replication study of 473 KD patients (p < 0.05). The SNP located at the CRP locus (rs12068753) demonstrated the most significant association with CRP in KD patients (beta = 4.73 and p = 1.20 × 10(-6) according to the stage 1 GWAS; beta = 3.65 and p = 1.35 × 10(-8) according to the replication study; beta = 3.97 and p = 1.11 × 10(-13) according to combined analysis) and explained 8.1% of the phenotypic variation observed. However, this SNP did not demonstrate any significant association with CRP in the general population (beta = 0.37 and p = 0.1732) and only explained 0.1% of the phenotypic variation in this instance. Furthermore, rs12068753 did not affect the development of coronary artery lesions or intravenous immunoglobulin resistance in KD patients. These results indicate that common variants in the CRP promoter can play an important role in the CRP levels in KD.
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 138-736, Korea.
authors.forename: Jae-Jung
authors.initials: JJ
authors.lastname: Kim
authors.forename: Sin Weon
authors.initials: SW
authors.lastname: Yun
authors.forename: Jeong Jin
authors.initials: JJ
authors.lastname: Yu
authors.forename: Kyung Lim
authors.initials: KL
authors.lastname: Yoon
authors.forename: Kyung-Yil
authors.initials: KY
authors.lastname: Lee
authors.forename: Hong-Ryang
authors.initials: HR
authors.lastname: Kil
authors.forename: Gi Beom
authors.initials: GB
authors.lastname: Kim
authors.forename: Myung Ki
authors.initials: MK
authors.lastname: Han
authors.forename: Min Seob
authors.initials: MS
authors.lastname: Song
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Lee
authors.forename: Jung Hye
authors.initials: JH
authors.lastname: Byeon
authors.forename: Saejung
authors.initials: S
authors.lastname: Sohn
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Hong
authors.forename: Gi Young
authors.initials: GY
authors.lastname: Jang
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis* / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D056426:Genetic Loci / Q000502:physiology*; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006105:Granulomatous Disease, Chronic; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood* / Q000235:genetics*; D019255:NADPH Oxidases / Q000172:deficiency; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide; D012709:Serum Albumin / Q000032:analysis
chemical_list: D006454:Hemoglobins; D012709:Serum Albumin; D002097:C-Reactive Protein; D019255:NADPH Oxidases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase