Kawasaki disease (KD) is an acute, self-limited vasculitis, mainly affecting children younger than 5 years old, with accompanying fever and signs of mucocutaneous inflammation. Intravenous immunoglobulin (IVIG) is the standard treatment for KD; however, ~15% of patients are resistant to IVIG treatment. To identify protein coding genetic variants influencing IVIG resistance, we re-analyzed our previous genome-wide association study (GWAS) data from 296 patients with KD, including 101 IVIG non-responders and 195 IVIG responders. Five nonsynonymous SNPs (nsSNPs) in five immune-related genes, including a previously reported SAMD9L nsSNP (rs10488532; p.Val266Ile), were associated with IVIG non-response (odds ratio [OR] = 1.89-3.46, P = 0.0109-0.0035). In a replication study of the four newly-identified nsSNPs, only one in the interleukin 16 (IL16) gene (rs11556218, p.Asn1147Lys) showed a trend of association with IVIG non-response (OR = 1.54, P = 0.0078). The same IL16 nsSNP was more significantly associated with IVIG non-response in combined analysis of all data (OR = 1.64, P = 1.25 × 10-4). Furthermore, risk allele combination of the IL16 CT and SAMD9L TT nsSNP genotypes exhibited a very strong effect size (OR = 9.19, P = 3.63 × 10-4). These results implicate IL16 as involved in the mechanism of IVIG resistance in KD.

中文翻译：

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川崎病中IL16 Asn1147Lys多态性与静脉免疫球蛋白抗性的相关性。

川崎病（KD）是一种急性的自限性血管炎，主要影响5岁以下的儿童，伴有发烧和皮肤粘膜炎症迹象。静脉免疫球蛋白（IVIG）是KD的标准治疗方法；但是，约15％的患者对IVIG治疗有抗药性。为了确定影响IVIG抵抗力的编码蛋白质的遗传变异，我们重新分析了我们以前的全基因组关联研究（GWAS）数据，该研究来自296位KD患者，包括101位IVIG无反应者和195位IVIG反应者。IVIG无应答与五个免疫相关基因中的五个非同义SNP（nsSNP）（包括先前报道的SAMD9L nsSNP（rs10488532; p.Val266Ile））相关（比值比[OR] = 1.89-3.46，P = 0.0109-0.0035 ）。在对四个新发现的nsSNP的复制研究中，白介素16（IL16）基因中只有一个（rs11556218，p.Asn1147Lys）表现出与IVIG无反应相关的趋势（OR = 1.54，P = 0.0078）。在所有数据的组合分析中，相同的IL16 nsSNP与IVIG无应答的关联更明显（OR = 1.64，P = 1.25×10-4）。此外，IL16 CT和SAMD9L TT nsSNP基因型的风险等位基因组合表现出非常强的效应大小（OR = 9.19，P = 3.63×10-4）。这些结果暗示IL16参与KD的IVIG抗性机制。IL16 CT和SAMD9L TT nsSNP基因型的高风险等位基因组合表现出非常强的效应大小（OR = 9.19，P = 3.63×10-4）。这些结果暗示IL16参与KD的IVIG抗性机制。IL16 CT和SAMD9L TT nsSNP基因型的高风险等位基因组合表现出非常强的效应大小（OR = 9.19，P = 3.63×10-4）。这些结果暗示IL16参与KD的IVIG抗性机制。