Genetic studies have identified several susceptibility genes for KD and its sequelae in different ethnic populations, including FCGR2A, CD40, ITPKC, FAM167A-BLK and CASP3, as well as genes influencing response to intravenous immunoglobulin (IVIG) and aneurysm formation such as FCGR3B, and transforming growth factor (TGF) β pathway genes.
We report two new loci, one at BLK (encoding B-lymphoid tyrosine kinase) and one at CD40, that are associated with Kawasaki disease at genome-wide significance (P < 5 × 10(-8)).
Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1.0 × 10<sup>-5</sup>), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10<sup>-11</sup>).
We report two new loci, one at BLK (encoding B-lymphoid tyrosine kinase) and one at CD40, that are associated with Kawasaki disease at genome-wide significance (P < 5 × 10(-8)).
CD40 rs1883832 is associated with decreased risk of Graves' disease, especially in Asian; CD40rs1883832 is associated with increased risk of multiple sclerosis; CD40 -1C>T (rs1883832) is not associated with the susceptibility of Hashimoto's thyroiditis, systemic sclerosis or Asthma; there is insufficient data to fully confirm the association between CD40rs1883832 and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Behçet's disease (BD), myasthenia gravis (MG), Crohn's disease (CD), ulcerative colitis (UC), Sarcoidosis, Fuch uveitis syndrome (FUS), Vogt-Koyanagi-Harada syndrome (VKH), Kawasaki disease (KD), giant cell arteritis (GCA) or Immune thrombocytopenia (ITP).
The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts.
Upon our previous genotyping data of 157 valid KD subjects, a genome-wide association study (GWAS) has been conducted among 11 (7%) CAA-developed KD patients to reveal five significant genetic variants passed pre-defined thresholds and resulted in two novel susceptibility protein-coding genes, which are NEBL (rs16921209 (P = 7.44 × 10(-9); OR = 32.22) and rs7922552 (P = 8.43 × 10(-9); OR = 32.0)) and TUBA3C (rs17076896 (P = 8.04 × 10(-9); OR = 21.03)).
For KD child patients, the complication with CAL or not has a close correlation with VEGF, PLT, D-dimer, and inflammatory factor; and VEGF, IL-6, PLT, and D-dimer are the important risk factors for KD complicated with CAL.
These findings suggest that the IL-10 (-627 A/C) promoter polymorphism might be a genetic marker for the risk of early coronary artery complication in KD.
Our data showed significant deviations between patients with Kawasaki disease and controls concerning the TNF -308 polymorphism genotype (GG: P = 0.0449) and allele (G,A: P = 0.0433) and -238 polymorphism genotype frequencies (AA: P = 0.0351).