Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Department of Cardiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Cytokine. 2018 Nov;111:216-221. doi: 10.1016/j.cyto.2018.08.029. Epub 2018 Sep 1.
Kawasaki disease is a multi-system vasculitis and a primary cause of acquired heart disease among children. Genetic factors may increase susceptibility to Kawasaki disease. TBXA2R is a G-protein-coupled receptor that participates in tissue inflammation and is associated with susceptibility to several diseases, but its relevance in Kawasaki disease is unclear. We genotyped TBXA2R (rs1131882 and rs4523) in 694 Kawasaki disease cases and 657 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the intensity of the associations. We found a significantly decreased risk of Kawasaki disease associated with TBXA2R rs4523 G variant genotypes (AG vs AA: adjusted OR = 0.788, 95%CI = 0.626-0.993; GG vs AA: adjusted OR = 0.459, 95%CI = 0.258-0.815; AG/GG vs AA: adjusted OR = 0.744, 95%CI = 0.595-0.929; GG vs AG/AA: adjusted OR = 0.497, 95% CI = 0.281-0.879). In the combined analysis of the two single-nucleotide polymorphisms (SNPs), we found that individuals with two unfavorable genotypes exhibited decreased risk for Kawasaki disease (adjusted OR = 0.754, 95%CI = 0.577-0.985) compared with those who did not have or one unfavorable genotypes. This cumulative effect on protection is effect-genotype dose-dependent (p = 0.022). Moreover, the combined analysis indicated that the two unfavorable genotypes were associated with a decreased risk of Kawasaki disease in children 12-60 months of age, females and the subgroup with non-coronary artery lesion (NCAL) formation compared with those who did not have or one unfavorable genotypes. In conclusion, the TBXA2R rs4523 G allele may contribute to protection against Kawasaki disease and decreased risk of coronary artery aneurysm complications in a southern Chinese population.
川崎病是一种多系统血管炎，也是儿童获得性心脏病的主要原因。遗传因素可能会增加川崎病的易感性。TBXA2R 是一种 G 蛋白偶联受体，参与组织炎症，与多种疾病的易感性有关，但它与川崎病的关系尚不清楚。我们在 694 例川崎病病例和 657 例健康对照中对 TBXA2R(rs1131882 和 rs4523)进行了基因分型。使用比值比(OR)和 95%置信区间(CI)来评估关联的强度。我们发现 TBXA2R rs4523 G 变异基因型与川崎病发病风险显著降低相关(AG 与 AA：调整 OR=0.788，95%CI=0.626-0.993；GG 与 AA：调整 OR=0.459，95%CI=0.258-0.815；AG/GG 与 AA：调整 OR=0.744，95%CI=0.595-0.929；GG 与 AG/AA：调整 OR=0.497，95%CI=0.281-0.879)。在两个单核苷酸多态性(SNPs)的联合分析中，我们发现与没有或一个不利基因型的个体相比，具有两个不利基因型的个体川崎病发病风险降低(调整 OR=0.754，95%CI=0.577-0.985)。这种保护作用的累积效应与基因型剂量呈依赖性(p=0.022)。此外，联合分析表明，与没有或一个不利基因型的个体相比，两个不利基因型与儿童 12-60 月龄、女性和非冠状动脉病变(NCAL)形成亚组的川崎病发病风险降低相关。总之，TBXA2R rs4523 G 等位基因可能有助于保护华南人群免受川崎病的侵害，并降低冠状动脉瘤并发症的风险。
