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.

Establishment of Kawasaki disease database based on metadata standard

“…The deposited data can be obtained for research by contacting KKDGC or KBN. The genotype data of significantly KD associated variants, including BLK (rs2736340) ( 22 ), CD40 (rs1883832), CRP (rs12068753) ( 23 ), and KCNN2 (rs17136627) ( 24 ) is also in this database. The detailed information on specific genetic variants can be found in our previous publications ( 22–24 ).…”

Association between the miRNA‐149 rs2292832 T>C polymorphism and Kawasaki disease susceptibility in a southern Chinese population

“…In the first genome‐wide association study (GWAS) for KD, variants of several genes (such as lnx1 , CAMK2D , ZFHX3 , CSMD1 , and tcp1 ) were suggested to be associated with KD susceptibility . In addition, SNPs in rs2254546, rs2857151, rs4813003, rs16921209, rs7922552, rs17076896, rs12068753, rs4786091, and rs2833195 and some SNPs in BLK , CD40 , and FCGR2A may be relevant to susceptibility, clinical presentations (such as CAA and CAL), laboratory data (such as CRP), treatment of KD, and gender in KD in GWASs …”

Combined Effects of Single Nucleotide Polymorphisms (SNPs) within C-reactive Protein (CRP) and Environmental Parameters on Risk and Prognosis for Diabetic Foot Osteomyelitis Patients

“…Based on genome-wide association studies (GWASs) relevant to CRP [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38], the SNPs that could affect serum level of CRP were selected and included in this investigation. We also included SNPs with a confirmed association with inflammatory disorders [39][40][41][42][43].…”