CD40Gene Polymorphisms Associated with Susceptibility and Coronary Artery Lesions of Kawasaki Disease in the Taiwanese Population

Abstract

Background. Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. Our previous studies showed expression of CD40 ligand on CD4+ T cells correlated to the coronary artery lesion (CAL) and disease progress in KD. Other studies from Japan suggested the role of CD40L in the pathogenesis of CAL, and this might help explain the excessive number of males affected with KD but cannot be reproduced by Taiwanese population. This study was conducted to investigate the CD40 polymorphism in KD and CAL formation. Methods. A total of 950 subjects (381 KD patients and 569 controls) were investigated to identify 2 tagging single-nucleotide polymorphisms (tSNPs) of CD40 (rs4810485 and rs1535045) by using the TaqMan allelic discrimination assay. Results. A significant association was noted with regards to CD40 tSNPs (rs1535045) between controls and KD patients (P = 0.0405, dominant model). In KD patients, polymorphisms of CD40 (rs4810485) showed significant association with CAL formation (P = 0.0436, recessive model). Haplotype analysis did not yield more significant results between polymorphisms of CD40 and susceptibility/disease activity of KD. Conclusions. This study showed for the first time that polymorphisms of CD40 are associated with susceptibility to KD and CAL formation, in the Taiwanese population.

Clinical significance of costimulatory molecules CD40/CD40L and CD134/CD134L in coronary heart disease

“…[ 33 ] Importantly, as the key hub of the inflammatory and immune responses in vivo, the CD40/CD40L system may be responsible for antigen presentation and immune response, and associate significantly with the activation of T lymphocytes and macrophages, thereby exerting critical biological roles in different cell types by the modulation of different signaling pathways. [ 34 , 35 ] With respect to the above, it was postulated in the present study that the combination of CD40 and CD40L might be partially involved in the development of CHD in view of their important effects implicated in activating immune cells and initiating the immune process. In this study, CD40/CD40L mRNA and expression levels were all increased in the CHD group when compared with the control group.…”

Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan

“…Genome-wide association analysis has enabled the discovery of novel genetic loci that contribute to KD susceptibility 10 11 12 13 14 15 . More recently, genetic susceptibility for the development of CAA formation has also been investigated using candidate gene analyses 11 16 21 22 23 24 25 26 27 28 29 30 . These studies have provided us with a preliminary genetic architecture of KD as well as of CAA formation therein.…”

“…Although the cause of KD remains unknown, many efforts have been made to decrease CAA formation in patients with KD by using aspirin and IVIG treatments. In addition, proposed candidate gene studies for CAA formation in KD have suggested the involvement of genetic factors including MICB , PELI1 , CASP3 , CD40 , MMP-3 , MMP-12 , HLA-B associated transcript 2, 3, and 5, ITPR3 , HLA-E , HLA-G , ITPKC , IL-10 , and angiotensin I converting enzyme ( ACE ) genes 11 16 21 22 23 24 25 26 27 28 29 30 . These candidate genes are involved in the immune-regulatory responses and cardiovascular-related pathogenesis that contribute to the susceptibility to and/or formation of CAA in KD.…”

Preventing coronary artery lesions in Kawasaki disease

“…KD may be caused by a combination of genetic background ( CD40 , BLK , ITPKC , FCGR2A , CD40L , CASP3 … etc.) [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , infectious agents (bacteria, virus, mycoplasma, etc.) [6] , [23] and immune response [24] , [25] .…”