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Ueta, M.,Sawai, H.,Sotozono, C.,Hitomi, Y.,Kaniwa, N.,Kim, M.K.,Seo, K.Y.,Yoon, K.C.,Joo, C.K.,Kannabiran, C.,Wakamatsu, T.H.,Sangwan, V.,Rathi, V.,Basu, S.,Ozeki, T.,Mushiroda, T.,Sugiyama, E.,Maekaw Mosby 2015 The Journal of allergy and clinical immunology Vol.135 No.6
Background: Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface, oral cavity, and genitals. These reactions are very rare but are often associated with inciting drugs, infectious agents, or both. Objective: We sought to identify susceptibility loci for cold medicine-related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement (SMI). Methods: A genome-wide association study was performed in 808 Japanese subjects (117 patients with CM-SJS/TEN with SMI and 691 healthy control subjects), and subsequent replication studies were performed in 204 other Japanese subjects (16 cases and 188 control subjects), 117 Korean subjects (27 cases and 90 control subjects), 76 Indian subjects (20 cases and 56 control subjects), and 174 Brazilian subjects (39 cases and 135 control subjects). Results: In addition to the most significant susceptibility region, HLA-A, we identified IKZF1, which encodes Ikaros, as a novel susceptibility gene (meta-analysis, rs4917014 [G vs T]; odds ratio, 0.5; P = 8.5 x 10<SUP>-11</SUP>). Furthermore, quantitative ratios of the IKZF1 alternative splicing isoforms Ik1 and Ik2 were significantly associated with rs4917014 genotypes. Conclusion: We identified IKZF1 as a susceptibility gene for CM-SJS/TEN with SMI not only in Japanese subjects but also in Korean and Indian subjects and showed that the Ik2/Ik1 ratio might be influenced by IKZF1 single nucleotide polymorphisms, which were significantly associated with susceptibility to CM-SJS/TEN with SMI.
Ueta, M.,Sawai, H.,Shingaki, R.,Kawai, Y.,Sotozono, C.,Kojima, K.,Yoon, K. C.,Kim, M. K.,Seo, K. Y.,Joo, C. K. Springer Science + Business Media 2017 Journal of human genetics Vol.62 No.4
<P>A genome-wide association study (GWAS) for cold medicine-related Stevens-Johnson syndrome (CM-SJS) with severe ocular complications (SOC) was performed in a Japanese population. A recently developed ethnicity-specific array with genome-wide imputation that was based on the whole-genome sequences of 1070 unrelated Japanese individuals was used. Validation analysis with additional samples from Japanese individuals and replication analysis using samples from Korean individuals identified two new susceptibility loci on chromosomes 15 and 16. This study might suggest the usefulness of GWAS using the ethnicity-specific array and genome-wide imputation based on large-scale whole-genome sequences. Our findings contribute to the understanding of genetic predisposition to CM-SJS with SOC.</P>
Hiroki Mieno,Kazuhito Yoneda,Nobuhiro Terao,Kengo Yoshii,Kentaro Kojima,Kenji Nagata,Chie Sotozono 대한안과학회 2020 Korean Journal of Ophthalmology Vol.34 No.4
Purpose: To investigate the efficacy of aflibercept for the treatment of diabetic macular edema via a treat-and-extend regimen. Methods: This prospective, single-center, open-label, interventional study involved 30 patients with a best-corrected visualacuity (BCVA) ≤0.6 and a central retinal thickness (CRT) ≥300 μm. The enrolled eyes each received a monthly intravitreal afliberceptinjection until the CRT decreased below 300 μm, upon which the administration interval was extended for 1 monthuntil the CRT once again increased to ≥300 μm. Main outcome measures were median BCVA and CRT at 6 and 12 monthsafter initiation of treatment via last observation carried forward analysis, the median number of injections over the 12months, and the effects on the diabetic retinopathy severity scale (DRSS) score of the patients who completed the 12-monthfollow-up period. Results: Of the 30 enrolled patients, 29 and 25 respectively completed the 6- and 12-month follow-up examinations. Frombaseline to 6 and 12 months after treatment initiation, the median BCVA (logarithm of the minimum angle of resolution) significantlyimproved from 0.52 to 0.30 and 0.35, respectively, and the median CRT significantly decreased from 439.5 to 268.5and 249.0 μm, respectively. The median number of injections over the 12-month follow-up period was 6.0. Compared tobaseline, the DRSS score at 12 months was improved by 2 steps in 16% of patients; in no cases did the DRSS score worsen orimprove by three steps or more. Conclusions: When administered in a treat-and-extend regimen, aflibercept is an effective treatment option for diabeticmacular edema.