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.
| Original language | English |
|---|---|
| Pages (from-to) | 438-444 |
| Number of pages | 7 |
| Journal | Pediatric Cardiology |
| Volume | 36 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2015 Jan 23 |
Fingerprint
Keywords
- C-reactive protein (CRP)
- Genome-wide association study (GWAS)
- Kawasaki disease (KD)
- Single nucleotide polymorphism (SNP)
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Cardiology and Cardiovascular Medicine
Cite this
Common Variants in the CRP Promoter are Associated with a High C-Reactive Protein Level in Kawasaki Disease. / Kim, Jae Jung; Yun, Sin Weon; Yu, Jeong Jin; Yoon, Kyung Lim; Lee, Kyung Yil; Kil, Hong Ryang; Kim, Gi Beom; Han, Myung Ki; Song, Min Seob; Lee, Hyoung Doo; Byeon, Jung Hye; Sohn, Saejung; Hong, Young Mi; Jang, Giyoung; Lee, Jong Keuk.
In: Pediatric Cardiology, Vol. 36, No. 2, 23.01.2015, p. 438-444.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Common Variants in the CRP Promoter are Associated with a High C-Reactive Protein Level in Kawasaki Disease
AU - Kim, Jae Jung
AU - Yun, Sin Weon
AU - Yu, Jeong Jin
AU - Yoon, Kyung Lim
AU - Lee, Kyung Yil
AU - Kil, Hong Ryang
AU - Kim, Gi Beom
AU - Han, Myung Ki
AU - Song, Min Seob
AU - Lee, Hyoung Doo
AU - Byeon, Jung Hye
AU - Sohn, Saejung
AU - Hong, Young Mi
AU - Jang, Giyoung
AU - Lee, Jong Keuk
PY - 2015/1/23
Y1 - 2015/1/23
N2 - 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.
AB - 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.
KW - C-reactive protein (CRP)
KW - Genome-wide association study (GWAS)
KW - Kawasaki disease (KD)
KW - Single nucleotide polymorphism (SNP)
UR - http://www.scopus.com/inward/record.url?scp=84943588821&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943588821&partnerID=8YFLogxK
U2 - 10.1007/s00246-014-1032-1
DO - 10.1007/s00246-014-1032-1
M3 - Article
C2 - 25266886
AN - SCOPUS:84943588821
VL - 36
SP - 438
EP - 444
JO - Pediatric Cardiology
JF - Pediatric Cardiology
SN - 0172-0643
IS - 2
ER -