Specific association of the rs6500265 and rs9933632 single-nucleotide polymorphisms in Japanese patients with antipyretic analgesic-related Stevens-Johnson syndrome and toxic epidermal necrolysis with severe ocular involvements.
Specific association of the rs6500265 and rs9933632 single-nucleotide polymorphisms in Japanese patients with antipyretic analgesic-related Stevens-Johnson syndrome and toxic epidermal necrolysis with severe ocular involvements.
复制标题
rs6500265 和 rs9933632 单核苷酸多态性在日本解热镇痛相关史蒂文斯-约翰逊综合征和严重眼部受累中毒性表皮坏死松解症患者中的特异性关联。
DOI：
10.1097/fpc.0000000000000324
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Saito Y.
中科院分区：
文献类型：
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作者：
Okamoto-Uchida Y;Nakamura R;Matsunaga K;Aihara M;Saito Y.
最近的一项研究使用专门为日本人群设计的单核苷酸多态性 (SNP) 基因分型微阵列，结合全基因组插补，显示了几种 SNP 与感冒药相关的史蒂文斯-约翰逊综合征 (SJS) 和中毒性表皮坏死松解症 (TEN) 以及严重眼部并发症之间的关联。然而，这些多态性是否与解热镇痛 (AA) 相关 SJS/TEN 的发生、严重眼部受累 (SOI) 的进展或与 AA 相关 SJS/TEN 和 SOI 表型相关，仍有待确定。为了更好地了解这些遗传标记的特征，我们比较了原始 SJS/TEN 患者组中这些 SNP 的等位基因和携带者频率：(a) 具有 SOIs 的 AA 相关 SJS/TEN，(b) 不具有 SOIs 的 AA 相关 SJS/TEN，以及 (c) 具有 SOIs 的 AA 不相关 SJS/TEN。 AA 相关的 SJS/TEN 和 SOI 被发现与 rs6500265 显着相关[等位基因频率：比值比 (OR)：2.18； 95%置信区间（CI）：1.30–3.65； P=0.0052；载波频率：OR：2.52； 95% CI：1.33–4.78； P= 0.058] 和 rs9933632（等位基因频率：OR：2.28：95% CI：1.37–3.79；P= 0.0032；载体频率：OR：2.76；95% CI：1.46–5.22；P= 0.0031）。相比之下，在没有 SOI 的 AA 相关 SJS/TEN 患者或未接受任何 AA 治疗的 SOI 患者中，这些 SNP 的等位基因和携带者频率与健康日本对照者相当。总的来说，我们的研究结果表明，rs6500265 和 rs9933632 SNP 可能是 AA 相关 SJS/TEN 与 SOI 的特异性标记，表明某些遗传背景导致了这种复杂综合征的病因学。
A recent study using the microarray for single-nucleotide polymorphisms (SNPs) genotyping specifically designed for the Japanese population in combination with genome-wide imputation showed the association of several SNPs with cold medicine-related Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with severe ocular complications. However, it remains to be determined whether these polymorphisms are associated with the onset of antipyretic analgesic (AA)-related SJS/TEN, the progression of severe ocular involvements (SOIs), or both AA-related SJS/TEN and SOI phenotypes. To gain a better understanding of the features of these genetic markers, we compared the allele and carrier frequencies of these SNPs among our original SJS/TEN patient groups:(a) AA-related SJS/TEN with SOIs,(b) AA-related SJS/TEN without SOIs, and (c) AA-unrelated SJS/TEN with SOIs. AA-related SJS/TEN with SOIs were found to be associated significantly with both rs6500265 [allele frequency: odds ratio (OR): 2.18; 95% confidence interval (CI): 1.30–3.65; P= 0.0052; carrier frequency: OR: 2.52; 95% CI: 1.33–4.78; P= 0.058] and rs9933632 (allele frequency: OR: 2.28: 95% CI: 1.37–3.79; P= 0.0032; carrier frequency: OR: 2.76; 95% CI: 1.46–5.22; P= 0.0031). In contrast, allele and carrier frequencies of these SNPs in patients with AA-related SJS/TEN without SOIs or with SOIs not treated with any AAs were comparable with those in healthy Japanese controls. Collectively, our findings indicate that the rs6500265 and rs9933632 SNPs could be specific markers for AA-related SJS/TEN with SOIs, suggesting that certain genetic backgrounds contribute toward the etiology of this complex syndrome.