Common Variants in the CRP Promoter are Associated with a High C-Reactive Protein Level in Kawasaki Disease

Jae Jung Kim, Sin Weon Yun, Jeong Jin Yu, Kyung Lim Yoon, Kyung Yil Lee, Hong Ryang Kil, Gi Beom Kim, Myung Ki Han, Min Seob Song, Hyoung Doo Lee, Jung Hye Byeon, Saejung Sohn, Young Mi Hong, Giyoung Jang, Jong Keuk Lee

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish
Pages (from-to)438-444
Number of pages7
JournalPediatric Cardiology
Volume36
Issue number2
DOIs
Publication statusPublished - 2015 Jan 23

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Mucocutaneous Lymph Node Syndrome
C-Reactive Protein
Single Nucleotide Polymorphism
Genome-Wide Association Study
Blood Sedimentation
Leukocyte Count
Genetic Loci
Intravenous Immunoglobulins
Aspartate Aminotransferases
Vasculitis
Alanine Transaminase
Platelet Count
Albumins
Coronary Vessels
Hemoglobins
Neutrophils
Fever
Biomarkers
Inflammation

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

Kim, J. J., Yun, S. W., Yu, J. J., Yoon, K. L., Lee, K. Y., Kil, H. R., ... Lee, J. K. (2015). Common Variants in the CRP Promoter are Associated with a High C-Reactive Protein Level in Kawasaki Disease. Pediatric Cardiology, 36(2), 438-444. https://doi.org/10.1007/s00246-014-1032-1

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 journalArticle

Kim, JJ, Yun, SW, Yu, JJ, Yoon, KL, Lee, KY, Kil, HR, Kim, GB, Han, MK, Song, MS, Lee, HD, Byeon, JH, Sohn, S, Hong, YM, Jang, G & Lee, JK 2015, 'Common Variants in the CRP Promoter are Associated with a High C-Reactive Protein Level in Kawasaki Disease', Pediatric Cardiology, vol. 36, no. 2, pp. 438-444. https://doi.org/10.1007/s00246-014-1032-1
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. / Common Variants in the CRP Promoter are Associated with a High C-Reactive Protein Level in Kawasaki Disease. In: Pediatric Cardiology. 2015 ; Vol. 36, No. 2. pp. 438-444.
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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.",
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AU - Kil, Hong Ryang

AU - Kim, Gi Beom

AU - Han, Myung Ki

AU - Song, Min Seob

AU - Lee, Hyoung Doo

AU - Byeon, Jung Hye

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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.

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