HLA-A*02:06 and PTGER3 polymorphism exert additive effects in cold medicine-related Stevens-Johnson syndrome with severe ocular complications.
HLA-A*02:06 and PTGER3 polymorphism exert additive effects in cold medicine-related Stevens-Johnson syndrome with severe ocular complications.
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DOI：
10.1038/hgv.2015.23
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发表时间：
2015
影响因子：
1.5
通讯作者：
Kinoshita S
中科院分区：
文献类型：
--
作者：
Ueta M;Tokunaga K;Sotozono C;Sawai H;Yoon KC;Kum Kim M;Yul Seo K;Joo CK;Tashiro K;Kinoshita S
我们之前报道过PTGER3（前列腺素E受体3 （EP3亚型））单核苷酸多态性（snp）与Stevens-Johnson综合征(SJS)/中毒性表皮坏死松解（TEN）伴严重眼部并发症（SOC）相关。我们还记录了大约80%的SJS/TEN患者在发病前几天内服用过感冒药，因此我们将他们指定为与感冒药相关的SJS/TEN （CM-SJS/TEN）患者。此外，我们还报道了TLR3多态性的HLA-A*02:06在SOC的SJS/TEN中发挥了更多的加性效应。本研究以CM-SJS/TEN的SOC为研究对象，分析了日本和韩国人群中PTGER3 snp与HLA-A*02:06的相关性以及PTGER3 snp与HLA-A*02:06之间的相互作用。在日本人群中，PTGER3 SNP rs1327464与CM-SJS/TEN与SOC的相关性最为显著（G vs A；比值比(OR)=0.232， P=7.92×10−10），我们发现HLA-A*02:06与高危基因型PTGER3 rs1327464 GA或AA之间存在加性效应交互作用（OR=10.8， P=2.56×10−7）。我们还发现韩国人CM-SJS/TEN与SOC和PTGER3 SNP rs1327464之间存在显著相关性（GG vs GA+AA， OR=0.246， P=0.00101），并且我们发现HLA-A*02:06与高危基因型PTGER3 rs1327464 GA或AA之间存在加性效应（OR=14.2， P=5.58×10−6）。
We previously reported that PTGER3 (prostaglandin E receptor 3 (subtype EP3)) single-nucleotide polymorphisms (SNPs) were associated with Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with severe ocular complications (SOC). We also documented that approximately 80% of our SJS/TEN patients had taken cold medicines within several days before disease onset, and we thus designated them cold medicine-related SJS/TEN (CM-SJS/TEN) patients. Moreover, we reported that HLA-A*02:06 with TLR3 polymorphisms exerted more than additive effects in SJS/TEN with SOC. In this study, we focused on CM-SJS/TEN with SOC and analyzed the association with PTGER3 SNPs and an interactive effect between PTGER3 SNPs and HLA-A*02:06 in not only the Japanese but also the Korean population. In the Japanese population, PTGER3 SNP rs1327464 was most significantly associated with CM-SJS/TEN with SOC (G versus A; odds ratio (OR)=0.232, P=7.92×10−10), and we found an interaction with additive effects between HLA-A*02:06 and the high-risk genotypes PTGER3 rs1327464 GA or AA (OR=10.8, P=2.56×10−7). We also found a significant association between Korean CM-SJS/TEN with SOC and PTGER3 SNP rs1327464 (GG versus GA+AA, OR=0.246, P=0.00101), and we detected an additive effect between HLA-A*02:06 and the high-risk genotypes PTGER3 rs1327464 GA or AA (OR=14.2, P=5.58×10−6).