Dataset Information

Association of promoter genetic variants in interleukin-10 and Kawasaki disease with coronary artery aneurysms.

ABSTRACT: BACKGROUND:Kawasaki disease (KD) is an acute, self-limited vasculitis in infants and young children. Interleukin-10 (IL-10) is a potent cytokine that exerts pleiotropic effects on immunoregulation and inflammation. Elevated IL-10 serum levels have been reported in the KD patients. METHODS:In this study, we investigated whether IL-10 genetic polymorphisms contribute to coronary artery aneurysm (CAA) development among KD patients in Taiwan. A total of 58 KD patients with CAA and 277 unrelated healthy children matched for sex and age were enrolled for this study. RESULTS:Higher G allele frequencies of IL-10 at -1082 position were observed in KD patients with CAA compared to the controls (P = 0.016, OR: 2.86, 95% CI, 1.17-6.98). In addition, higher IL-10 GCC haplotype frequencies were also observed in KD patients with CAA (P = 0.016, OR: 2.85, 95% CI, 1.17-6.98). CONCLUSION:Our data support the possibility that IL-10 gene polymorphisms may be related with CAA development of KD in Taiwanese population.

SUBMITTER: Lin YJ

PROVIDER: S-EPMC6807467 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Association of promoter genetic variants in interleukin-10 and Kawasaki disease with coronary artery aneurysms.

Lin Ying-Ju YJ Lan Yu-Ching YC Lai Chih-Ho CH Lin Ting-Hsu TH Huang Shao-Mei SM Liao Chiu-Chu CC Lin Cheng-Wen CW Hung Chien-Hui CH Tien Ni N Liu Xiang X Chien Wen-Kuei WK Chen Jin-Hua JH Tsai Fuu-Jen FJ

Journal of clinical laboratory analysis 20140322 6

<h4>Background</h4>Kawasaki disease (KD) is an acute, self-limited vasculitis in infants and young children. Interleukin-10 (IL-10) is a potent cytokine that exerts pleiotropic effects on immunoregulation and inflammation. Elevated IL-10 serum levels have been reported in the KD patients.<h4>Methods</h4>In this study, we investigated whether IL-10 genetic polymorphisms contribute to coronary artery aneurysm (CAA) development among KD patients in Taiwan. A total of 58 KD patients with CAA and 277 ...[more]

PMID: 24659220

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Project description:Importance:Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). Objective:To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. Design, Setting, and Participants:This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. Main Outcomes and Measures:The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ?5 to <10; actual internal diameter, <8 mm), and large (z score, ?10 or ?8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Results:Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P?<?.001) and 100%, 100%, and 75% in women (P?<?.001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P?<?.001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P?<?.001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. Conclusions and Relevance:Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

Project description:Kawasaki Disease (KD) is the leading cause of acquired pediatric heart disease. A subset of KD patients develops aneurysms in the coronary arteries, leading to increased risk of thrombosis and myocardial infarction. Currently, there are limited clinical data to guide the management of these patients, and the hemodynamic effects of these aneurysms are unknown. We applied patient-specific modeling to systematically quantify hemodynamics and wall shear stress in coronary arteries with aneurysms caused by KD. We modeled the hemodynamics in the aneurysms using anatomic data obtained by multi-detector computed tomography (CT) in a 10-year-old male subject who suffered KD at age 3 years. The altered hemodynamics were compared to that of a reconstructed normal coronary anatomy using our subject as the model. Computer simulations using a robust finite element framework were used to quantify time-varying shear stresses and particle trajectories in the coronary arteries. We accounted for the cardiac contractility and the microcirculation using physiologic downstream boundary conditions. The presence of aneurysms in the proximal coronary artery leads to flow recirculation, reduced wall shear stress within the aneurysm, and high wall shear stress gradients at the neck of the aneurysm. The wall shear stress in the KD subject (2.95-3.81 dynes/sq cm) was an order of magnitude lower than the normal control model (17.10-27.15 dynes/sq cm). Particle residence times were significantly higher, taking 5 cardiac cycles to fully clear from the aneurysmal regions in the KD subject compared to only 1.3 cardiac cycles from the corresponding regions of the normal model. In this novel quantitative study of hemodynamics in coronary aneurysms caused by KD, we documented markedly abnormal flow patterns that are associated with increased risk of thrombosis. This methodology has the potential to provide further insights into the effects of aneurysms in KD and to help risk stratify patients for appropriate medical and surgical interventions.

Dataset Information

Association of promoter genetic variants in interleukin-10 and Kawasaki disease with coronary artery aneurysms.

Publications

Association of promoter genetic variants in interleukin-10 and Kawasaki disease with coronary artery aneurysms.

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