Pioneering Research to Elucidate the Pathogenic Mechanism and Genetic Susceptibility of Stevens Johnson Syndrome/Toxic Epidermal Necrolysis

阐明史蒂文斯约翰逊综合征/中毒性表皮坏死松解症致病机制和遗传易感性的开创性研究

• 批准号: 22390325
• 负责人: SOTOZONO Chie
• 金额: $ 12.15万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390325/
• 关键词: Stevens-Johnson 症候群; 眼合併症; 遺伝子多型; 遺伝子間相互作用; 自然免疫異常; Stevens-Johnson症候群; 中毒性表皮壊死融解症; 全ゲノム解析; PTGER3遺伝子; prostaglandin E receptor 3 (EP3); 眼表面炎症; 非ステロイド系解熱鎮痛薬(NSAID); 重症薬疹; ゲノム解析; プロテオミクス; 自然免疫; サイトカイン

The purpose of this present study was to perform a Genome-Wide Association Study (GWAS) in order to elucidate in greater detail the pathophysiology of Stevens Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) with severe ocular surface complications. Our GWAS findings revealed 6 single-nucleotide polymorphisms (SNPs) (rs17131450, rs5702, rs1325949, rs7543182, rs7555874, and rs4147114) in prostaglandin E receptor 3 (EP3) that are significantly associated with SJS/TEN. When we looked for the expression of EP3 in the conjunctival epithelium of SJS/TEN patients with severe ocular surface complications, we did not find EP3 protein. On the other hand, the EP3 protein was present in the conjunctival epithelium of the control patients with conjunctivochalasis or pterygium. Moreover, we found a variable with SJS genetic susceptibility effects involved in the locus-pairs of genes PTGER3-TLR3 and HLA-A*0206-TLR3.

本研究的目的是进行全基因组关联研究（GWAS），以更详细地阐明史蒂文斯约翰逊综合征/中毒性表皮坏死松解症（SJS/TEN）伴严重眼表并发症的病理生理学。我们的GWAS研究结果揭示了前列腺素E受体3（EP 3）中与SJS/TEN显著相关的6个单核苷酸多态性（SNP）（rs 17131450、rs 5702、rs 1325949、rs7543182、rs7555874和rs 4147114）。当我们在有严重眼表并发症的SJS/TEN患者的结膜上皮中寻找EP 3的表达时，我们没有发现EP 3蛋白。另一方面，EP 3蛋白存在于结膜松弛症或翼状胬肉的对照患者的结膜上皮中。此外，我们发现一个变量与SJS的遗传易感性效应涉及基因PTGER 3-TLR 3和HLA-A*0206-TLR 3的位点对。

项目成果

Etiologic Features of Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) with Ocular Involvement

史蒂文斯-约翰逊综合征 (SJS) 和眼部受累的中毒性表皮坏死松解症 (TEN) 的病因学特征

• 发表时间: 2012
• 作者: Sotozono C;Ueta M;Kinoshita S;Kitami A;Iijima M;Aihara M;Ikezawa Z;Kano Y;Shiohara T;Shirakata Y;Sakabayashi S;Matsubara Y;Hashimoto K
• 通讯作者: Hashimoto K

HLA-B*1511 is a risk factor for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients

• DOI: 10.1111/j.1528-1167.2010.02766.x
• 发表时间: 2010-12-01
• 期刊: EPILEPSIA
• 影响因子: 5.6
• 作者: Kaniwa, Nahoko;Saito, Yoshiro;Hasegawa, Ryuichi
• 通讯作者: Hasegawa, Ryuichi

Association between prostaglandin E receptor 3 polymorphisms and Stevens-Johnson syndrome identified by means of a genome-wide association study

• DOI: 10.1016/j.jaci.2010.08.007
• 发表时间: 2010-12-01
• 期刊: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
• 影响因子: 14.2
• 作者: Ueta, Mayumi;Sotozono, Chie;Kinoshita, Shigeru
• 通讯作者: Kinoshita, Shigeru

網膜における血管新生に関連する遺伝子の網羅的発現解析.

视网膜血管生成相关基因的综合表达分析。

• 发表时间: 2012
• 作者: 足立博子;丸山悠子;米田一仁;丸山和一;木下茂;中野正和;田代啓
• 通讯作者: 田代啓

Earlier is Better for the Treatment of Stevens-Johnson Syndrom

史蒂文斯-约翰逊综合症越早治疗越好

• 发表时间: 2012
• 作者: Yokoi T;Toriyama N;Yamane T;Nakayama Y;Nishina S;Azuma N;Ueta M
• 通讯作者: Ueta M