CD40 ligand gene and Kawasaki disease

Abstract

Kawasaki disease (KD) is an acute systemic vasculitis syndrome of infants and young children. Although its etiology is largely unknown, epidemiological findings suggest that genetic factors play a role in the pathogenesis of KD. To identify genetic factors, affected sib-pair analysis has been performed. One of the identified peaks was located on the Xq26 region. A recent report of elevated expression of CD40 ligand (CD40L), which maps to Xq26, during the acute-phase KD, and its relationship to the development of coronary artery lesions (CAL) prompted us to screen for polymorphism of CD40L and to study the association of the gene to KD. A newly identified SNP in intron 4 (IVS4 þ 121 A4G) is marginally overrepresented in KD patients as compared to controls (109/602, 18.1 vs 111/737, 15.1%). When male KD patients with CAL were analyzed as a patient group, the SNP was significantly more frequent than in controls (15/58, 25.9%, vs 111/737, 15.1%, OR ¼ 2.0, 95% CI ¼ 1.07 -3.66; P ¼ 0.030). Interestingly, this variation was extremely rare in a control Caucasian population (1/145, 0.7%). Our results suggest a role of CD40L in the pathogenesis of CAL and might explain the excess of males affected with KD.

Polymorphisms of transforming growth factor-β signaling pathway and Kawasaki disease in the Taiwanese population

“…Although incidence of KD varies in different ethnic population, several lines of evidence have indicated the significant association between genetic polymorphisms and the susceptibility of KD. For example, polymorphisms in the genes including monocyte chemoattractant protein 1, 10 IL-10, 11 CD40L, 12 IL-4, 13 CASP3, 14,15 IL-18, 16 HLA-E, 17 C-C chemokine receptor 5 18 and inositol 1,4,5-trisphosphate 3-kinase C 19,20 have been reported to be involved in the development of KD. However, only few genes from these studies could be deduced in the second populations that support the hypothesis that multiple polymorphic alleles influence the susceptibility and clinical phenotypes of KD.…”

A genomewide linkage analysis of Kawasaki disease: evidence for linkage to chromosome 12

“…Responsiveness to immunoglobulin therapy and/or vascular wall fragility to immune insults could be also determined by genetic factors that could predict disease outcome, if clarified. Applying a positional candidate gene approach to the preliminary results of this linkage study, we have already identified an SNP within the CD40 ligand gene on chromosome X that is associated with coronary artery lesions in (Onouchi et al 2004). Although only a few concordant sib pair cases of coronary artery lesions were involved in the present study, other linkage peaks observed may also represent loci for susceptibility to cardiac complication.…”

Genetic polymorphisms in Kawasaki disease

“…Jin [58] Tumor necrosis factor-alpha TNF-alpha 6p21.3 CAL Cheung [59] Quasney [49] CD40 ligand CD40L Xq26 CAL Onouchi [33] Huang [77] www.nature.com/aps Kuo HC et al Acta Pharmacologica Sinica npg ORAI1 tSNPs was found. Additionally, there is no association between ORAI1 polymorphisms and CAL formation or IVIG treatment responses [69] .…”

“…For example, a number of genes have been reported to have significant associations with the susceptibility to KD in different populations. For instance, single nucleotide polymorphisms (SNPs) in the monocyte chemoattractant protein 1 (MCP-1) [29] , IL-10 [30][31][32] , CD40L [33] , IL-4 [26] , CASP3 [20,34] , IL-18 [35] , IL-1B [36] , HLA-E [37] , C-C chemokine receptor 5 (CCR5) [38] , and inositol 1, 4, 5-trisphosphate 3-kinase C (ITPKC) [21,39] have been reported to be associated with the development of KD. In early 2011, Shimizu et al [12] first reported that genetic polymorphisms of TGFB2, TGFBR2, and SMAD3 are associated with susceptibility to Kawasaki disease and the development of coronary artery lesions.…”