Susceptibility genes for Kawasaki disease: toward implementation of personalized medicine.
ABSTRACT Kawasaki disease (KD) is an acute systemic vasculitis syndrome, which primarily affects in children under the age of 5 years. In 20-25% of cases, if untreated, coronary artery lesions develop, making KD the leading cause of acquired heart disease in children in both Japan and the United States. Since 1970, 19 nationwide surveys of KD in Japan have been conducted every 2 years and the data are stored in a database. Even though the etiology of KD remains unknown, despite enthusiastic research spanning more than 40 years, we have learnt a great deal about KD from this enormous database. These 19 epidemiologic studies indicate a strong genetic influence on the disease susceptibility, prompting us and other researchers to identify the responsible genes for KD by applying either the candidate gene approach or the genome-wide approach. We have employed a genome-wide linkage study using affected sibling pair data of KD in Japan and have identified several susceptibility loci. Further analysis focusing on a region of chromosome 19, where one of the linked loci was detected, identified a predisposing gene, which codes inositol 1,4,5-trisphosphate 3-kinase C (ITPKC). In this review, we summarize the cumulative knowledge regarding KD, and then outline our hypothesis of the role ITPKC plays in KD susceptibility and our trial that aims toward the implementation of personalized medicine for KD.
SourceAvailable from: Gholamhossein Ajami[Show abstract] [Hide abstract]
ABSTRACT: Kawasaki disease (KD) clinically presents as a systemic vasculitis syndrome with significant cardiovascular involvement. With different incidence among different ethnic groups, the role of certain human leukocyte antigens and their products has been considered as a crucial predisposing factor in the immune responses in this disease. We determined the distribution of human leukocyte antigens type B for 90 Iranian patients with Kawasaki disease in order to evaluate a possible association between these antigens and this disease in our area. We used the polymerase chain reaction (PCR) sequence specific primers (PCR-SSP) technique for antigen typing. Distribution of these antigens for 89 healthy Iranians used as control. Findings : While 7 (3.9%) of our patients were positive for human leukocyte antigen type B 40(*), there were 18 (10.1%) subjects from the control group who had this antigen with statistically significant difference between patients and control group (CI= 95%, RR=1.15 and P= 0.02). Data were analyzed by Pearson chi-square test and Fisher's exact test. SPSS version 15 was used for statistical analysis and a P value less than 0.05 considered statistically significant The presence of higher frequency of allele type-B40(*) in the control group may represent a protective role for this antigen with resultant decreased susceptibility to KD in our area.Iranian Journal of Pediatrics 08/2014; 24(4):359-64. · 0.34 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Coronary artery vasculitis is rare and comprises an array of inflammatory diseases. It often results in severe and life-threatening complications, including coronary artery aneurysm, coronary artery stenosis, intraluminal thrombosis, and microcirculation abnormalities. These may occur at a young age and are often silent in the early phases. Invasive coronary angiography is the gold standard for diagnosing coronary artery disease (CAD); however, multi-detector computed tomography (MDCT) is now widely regarded as a powerful non-invasive tool for the detection of CAD. It is important for clinicians to recognize the various CT findings associated with coronary artery vasculitis in order to promote accurate diagnosis and proper patient management. The purpose of this article is to present an overview of the conditions associated with coronary artery vasculitis, with an emphasis on etiology and cardiac MDCT diagnosis of CAD. Cardiac MDCT is clinically useful and can provide information for the accurate diagnosis and treatment of coronary vasculitis.The international journal of cardiovascular imaging 04/2015; DOI:10.1007/s10554-015-0652-8 · 2.32 Impact Factor
Frontiers in Bioscience 01/2013; 18(3):919. DOI:10.2741/4153 · 4.25 Impact Factor