Genome-wide association studies in Kawasaki disease (KD)
| Gene | Locus | Population | Biological significance | References |
|---|---|---|---|---|
| FCGR2A (encodes low-affinity immunoglobulin gamma Fc region receptor II-a) | 1q23 | European, Asian | The involvement of FCGR2A in susceptibility to KD highlights the importance of IgG receptors in the pathogenesis of this inflammatory disease and provides a biological basis for the use of intravenous immunoglobulin for treatment. | 37 |
| ITPKC (inositol 1,4,5-trisphosphate 3-kinase C) | 19q23 | Japanese, American | ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signalling pathway, and the C allele may contribute to immune hyper-reactivity in KD. This finding provides new insights into the mechanisms of immune activation in KD and emphasises the importance of activated T cells in the pathogenesis of this vasculitis | 36 |
| ABCC4 (ATP-binding cassette, subfamily C, member 4) | 13q32 | European, American, Australian | ABCC4 is a multifunctional cyclic nucleotide transporter that stimulates the migratory capacity of dendritic cells and a mediator of prostaglandin efflux from human cells inhibited by non-steroidal anti-inflammatory medications such as aspirin. | 38 |
| Intergenic region between FAM167A and BLK | 8p22-23 | Japanese | Variations in the FAM167ABLK region have been associated with several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. BLK encodes B-lymphoid tyrosine kinase, a Src family tyrosine kinase downstream of the B-cell receptor. Mechanism in KD pathogenesis unknown. | 34 |
| CD40 | 20q12–q13.2 | Taiwanese, Japanese | CD40 L is expressed on the surface of CD4 T-cells and platelets, and engages with CD40 expressed on the surface of antigen-presenting cells or endothelial cells. Transduces signals related to cell activation or development. Elevated expression of CD40 L during acute-phase KD, and significantly higher expression in KD patients with CAA have been reported. | 34 |
CAA, coronary artery aneurysms; NFAT, nuclear factor of activated T cells.