Table_4_ITPKC polymorphism (rs7251246 T > C), coronary artery aneurysms, and thrombosis in patients with Kawasaki disease in a Southern Han Chinese population.docx

ObjectivesKawasaki disease (KD) is a commonly acquired pediatric systemic vasculitis disease resulting in coronary artery aneurysm (CAA). The relationship between the ITPKC polymorphism (rs7251246) and the severity and susceptibility to KD in the Han Chinese population in Southern China remains unclear.
MethodsWe enrolled 262 children as controls and 221 children with KD (46 [20.8%] with intravenous immunoglobulin resistance and 82 [37.1%] with CAA). The relationship between the ITPKC rs7251246 polymorphism, KD susceptibility, and CAA formation was investigated.
ResultsWhile the ITPKC rs7251246 T>C polymorphism was not significantly associated with KD susceptibility, it was significantly related to the CAA risk in children with KD [CC/CT vs. TT: adjusted odds ratio [OR] 2.089, 95% confidence interval [CI] 1.085–4.020]. Male children with the rs7251246 CT/TT genotype had a significantly lower risk of thrombosis [CT/TT vs. CC: adjusted OR 0.251, 95% CI 0.068–0.923]. Children with KD, especially those with CAA, had significantly downregulated ITPKC mRNA compared to healthy children. ITPKC mRNA levels were lower in children with CAA who developed thrombosis (P=0.039). In children with KD, the CC genotype showed lower mRNA levels of ITPKC (P=0.035).
ConclusionThe ITPKC rs7251246 T>C polymorphism may be a risk factor for CAA and thrombosis in children with KD in the Han Chinese population, likely due to differences in mature mRNA levels caused by interference of RNA splicing. Dual antiplatelet therapy for thrombosis is recommended for male children with the rs7251246 CC genotype.

研究目标：川崎病（Kawasaki disease, KD）是一种常见的获得性儿童全身性血管炎，可引发冠状动脉瘤（coronary artery aneurysm, CAA）。目前中国南方汉族人群中ITPKC基因多态性（rs7251246）与KD易感性及病情严重程度的关联尚不明确。
研究方法：本研究纳入262名儿童作为对照，221名KD患儿（其中46例[20.8%]为静脉注射免疫球蛋白耐药患儿，82例[37.1%]合并冠状动脉瘤），探讨ITPKC rs7251246多态性与KD易感性及CAA发生的关联。
研究结果：ITPKC rs7251246 T>C多态性与KD易感性无显著关联，但与KD患儿的CAA风险显著相关[CC/CT基因型 vs TT基因型：校正后比值比（odds ratio, OR）=2.089，95%置信区间（confidence interval, CI）=1.085~4.020]。携带rs7251246 CT/TT基因型的男性KD患儿血栓形成风险显著降低[CT/TT vs CC：校正OR=0.251，95%CI=0.068~0.923]。与健康儿童相比，KD患儿（尤其是合并CAA者）的ITPKC mRNA表达水平显著下调；合并血栓形成的CAA患儿ITPKC mRNA水平更低（P=0.039）。在KD患儿中，CC基因型携带者的ITPKC mRNA水平更低（P=0.035）。
研究结论：中国南方汉族人群中，ITPKC rs7251246 T>C多态性可能是KD患儿发生CAA及血栓的风险因素，其潜在机制可能与RNA剪接干扰导致的成熟mRNA水平差异有关。对于携带rs7251246 CC基因型的男性KD患儿，建议采用双联抗血小板治疗预防血栓形成。