A molecular epidemiological study of respiratory viruses detected in Japanese children with acute wheezing illness.

BACKGROUND: Recent studies strongly suggest that some respiratory viruses are associated with the induction of acute wheezing and/or exacerbation of bronchial asthma. However, molecular epidemiology of these viruses is not exactly known. METHODS: Using PCR technology, we attempted to detect various respiratory viruses from 115 Japanese children. Furthermore, the detected viruses were subjected to homology, pairwise distance, and phylogenetic analysis. RESULTS: Viruses were detected from 99 (86.1%) patients. Respiratory syncytial virus (RSV) alone and human rhinovirus (HRV) alone were detected in 47 (40.9%) and 36 (31.3%) patients, respectively. Both RSV and HRV were detected in 14 (12.2%) patients. Human metapneumovirus (HMPV) alone and human parainfluenza virus (HPIV) alone were detected in 1 (0.9%) patient each, respectively. Homology and phylogenetic analyses showed that the RSV and HRV strains were classified into genetically diverse species or subgroups. In addition, RSV was the dominant virus detected in patients with no history of wheezing, whereas HRV was dominant in patients with a history of wheezing. CONCLUSIONS: The results suggested that these genetically diverse respiratory viruses, especially RSV and HRV, might be associated with wheezing in Japanese children.

ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms.

Kawasaki disease is a pediatric systemic vasculitis of unknown etiology for which a genetic influence is suspected. We identified a functional SNP (itpkc_3) in the inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene on chromosome 19q13.2 that is significantly associated with Kawasaki disease susceptibility and also with an increased risk of coronary artery lesions in both Japanese and US children. Transfection experiments showed that the C allele of itpkc_3 reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca2+/NFAT signaling pathway, and the C allele may contribute to immune hyper-reactivity in Kawasaki disease. This finding provides new insights into the mechanisms of immune activation in Kawasaki disease and emphasizes the importance of activated T cells in the pathogenesis of this vasculitis.

CD40 ligand gene and Kawasaki disease.

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+121 A>G) is marginally over-represented 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=2.0, 95% CI=1.07-3.66; P=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.