HMGB1 gene polymorphism is associated with coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease
HMGB1 gene polymorphism is associated with coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease
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DOI：
10.1093/rheumatology/key356
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发表时间：
2019-05-01
期刊：
影响因子：
5.5
通讯作者：
Kim, Dong Soo
中科院分区：
文献类型：
--
作者：
Ahn, Jong Gyun;Bae, Yoonsun;Kim, Dong Soo
目标.川崎（KD）是一种病因不明的急性全身性血管炎，影响婴幼儿。最近的报告，在KD的急性期血清高迁移率族蛋白1（HMGB 1）水平升高，其关系到对IVIG治疗反应不良，提示HMGB 1多态性与KD的可能关联。我们研究了HMGB 1基因多态性、KD易感性、冠状动脉病变和KD对IVIG治疗反应之间的关系。进行HMGB 1基因的全基因组测序以鉴定致病变体。采用连锁不平衡分析方法筛选HMGB 1基因的两个标记单核苷酸多态性。采用TaqMan等位基因识别技术对468名受试者（265名KD患者和203名对照）的标记单核苷酸多态性进行基因分型。HMGB 1单核苷酸多态性与川崎病易感性无关。然而，在KD患者中，在隐性模型中，rs 1412125与冠状动脉病变形成显著相关（GG vs AA + GA：比值比= 4.98，95%CI = 1.69 - 14.66，P = 0.005）。rs 1412125与IVIG隐性耐药（GG vs AA + GA：OR = 4.11，95%CI = 1.38 ~ 12.23，P = 0.017）和等位基因耐药（G vs A：OR = 1.80，95%CI = 1.06 ~ 3.06，P = 0.027）相关。HMGB 1基因rs 1412125可能是KD患者冠状动脉病变和IVIG抵抗的危险因素。
Objectives. Kawasaki disease (KD) is an acute systemic vasculitis of unknown aetiology that affects infants and young children. Recent reports of elevated serum high mobility group box 1 (HMGB1) level during the acute phase of KD and its relationship to poor response to IVIG treatment suggest a possible association of HMGB1 polymorphisms with KD. We investigated the association between the polymorphisms of the HMGB1 gene, KD susceptibility, coronary artery lesions, and KD response to IVIG treatment.Methods. Whole genome sequencing of the HMGB1 gene was performed to identify causative variants. Two tagging single nucleotide polymorphisms of the HMGB1 gene were selected using linkage disequilibrium analysis. The tagging single nucleotide polymorphisms were genotyped using the TaqMan Allelic Discrimination assay in a total of 468 subjects (265 KD patients and 203 controls).Results. The HMGB1 single nucleotide polymorphisms were not associated with KD susceptibility. However, in KD patients, there was a significant association of rs1412125 with coronary artery lesions formation in the recessive model (GG vs AA + GA: odds ratio = 4.98, 95% CI = 1.69 - 14.66, P = 0.005). In addition, rs1412125 was associated with IVIG resistance in the recessive (GG vs AA + GA: odds ratio = 4.11, 95% CI = 1.38 - 12.23, P = 0.017) and allelic models (G vs A: odds ratio = 1.80, 95% CI = 1.06 - 3.06, P = 0.027).Conclusion. The rs1412125 in HMGB1 might be a risk factor for the development of coronary artery lesions and IVIG resistance in KD patients.