Department of Cardiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Clinical Lab, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
Cardiovasc Ther. 2020 Mar 10;2020:3568608. doi: 10.1155/2020/3568608. eCollection 2020.
Children with Kawasaki disease (KD) resistant to intravenous immunoglobulin (IVIG) have a higher incidence of coronary artery lesions (CAL). Despite the association between Purinergic receptor P2Y12 (P2RY12) polymorphism, KD genetic susceptibility, and CAL complications being proved, few studies have assessed the relationship between P2RY12 polymorphisms and IVIG resistance in patients with KD. We recruited 148 KD patients with IVIG resistance and 611 with IVIG sensitivity and selected five P2RY12 polymorphisms: rs9859538, rs1491974, rs7637803, rs6809699, and rs2046934. A significant difference in the genotype distributions between patients was only observed for the rs6809699 A > C polymorphism (AC vs. AA: adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.27-0.84, =0.011; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27-0.83, =0.0084). After adjusting for age and gender, the carriers of the rs6809699 C allele had OR of 0.44 to 0.49 for IVIG sensitivity (AC vs. AA: adjusted OR = 0.48, 95% confidence interval (CI) = 0.27-0.84, =0.011; AC/CC vs. AA: adjusted OR = 0.47, 95% CI = 0.27-0.83, =0.0084) compared to the carriers of a rs6809699 AA genotype, suggesting the protective effect of this SNP against IVIG resistance. Moreover, individuals with all five protective polymorphisms experienced a significantly decreased IVIG resistance compared to that of individuals with up to three protective polymorphisms (adjusted OR = 0.27, 95% CI = 0.13-0.57, =0.0006). Our results suggest that the P2RY12 rs6809699 polymorphism could be used as a biomarker to predict IVIG resistance in KD patients.
儿童川崎病（KD）对静脉注射免疫球蛋白（IVIG）耐药的患者发生冠状动脉病变（CAL）的发生率更高。尽管已经证明嘌呤能受体 P2Y12（P2RY12）多态性、KD 遗传易感性和 CAL 并发症之间存在关联，但很少有研究评估 P2RY12 多态性与 KD 患者 IVIG 耐药之间的关系。我们招募了 148 例 KD 患者，其中 IVIG 耐药患者 148 例，IVIG 敏感患者 611 例，选择了 5 个 P2RY12 多态性：rs9859538、rs1491974、rs7637803、rs6809699 和 rs2046934。仅 rs6809699 A> C 多态性在患者的基因型分布中存在显著差异（AC 与 AA：调整后的优势比（OR）=0.48，95%置信区间（CI）=0.27-0.84，=0.011；AC/CC 与 AA：调整后的 OR=0.47，95%CI=0.27-0.83，=0.0084）。在调整年龄和性别后，携带 rs6809699 C 等位基因的个体对 IVIG 敏感性的 OR 为 0.44 至 0.49（AC 与 AA：调整后的 OR=0.48，95%CI=0.27-0.84，=0.011；AC/CC 与 AA：调整后的 OR=0.47，95%CI=0.27-0.83，=0.0084），而携带 rs6809699 AA 基因型的个体则为 IVIG 耐药性的保护作用，提示该 SNP 对 IVIG 耐药性具有保护作用。此外，与携带 3 个以上保护性多态性的个体相比，携带所有 5 个保护性多态性的个体发生 IVIG 耐药的风险显著降低（调整后的 OR=0.27，95%CI=0.13-0.57，=0.0006）。我们的研究结果表明，P2RY12 rs6809699 多态性可作为预测 KD 患者 IVIG 耐药的生物标志物。
