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Trans-ethnic study confirmed independent associations of HLA-A02:06 and HLA-B44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications.

ABSTRACT: Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes. Cold medicines including non-steroidal anti-inflammatory drugs and multi-ingredient cold medications are reported to be important inciting drugs. Recently, we reported that cold medicine related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement including severe ocular surface complications (SOC) is associated with HLA-A*02:06 and HLA-B*44:03 in the Japanese. In this study, to determine whether HLA-B*44:03 is a common risk factor for CM-SJS/TEN with SOC in different ethnic groups we used samples from Indian, Brazilian, and Korean patients with CM-SJS/TEN with SOC, and investigated the association between CM-SJS/TEN with SOC and HLA-B*44:03 and/or HLA-A*02:06. We found that HLA-B*44:03 was significantly associated with CM-SJS/TEN with SOC in the Indian and Brazilian but not the Korean population, and that HLA-A*02:06 might be weakly associated in the Korean- but not the Indian and Brazilian population.

SUBMITTER: Ueta M

PROVIDER: S-EPMC4124463 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Trans-ethnic study confirmed independent associations of HLA-A02:06 and HLA-B44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications.

Ueta Mayumi M Kannabiran Chitra C Wakamatsu Tais Hitomi TH Kim Mee Kum MK Yoon Kyung-Chul KC Seo Kyoung Yul KY Joo Choun-Ki CK Sangwan Virender V Rathi Varsha V Basu Sayan S Shamaila Almas A Lee Hyo Seok HS Yoon Sangchul S Sotozono Chie C Gomes José Álvaro Pereira JÁ Tokunaga Katsushi K Kinoshita Shigeru S

Scientific reports 20140807

Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes. Cold medicines including non-steroidal anti-inflammatory drugs and multi-ingredient cold medications are reported to be important inciting drugs. Recently, we reported that cold medicine related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement including severe ocular surface complications (SOC) is associated with HLA-A*02: ...[more]

PMID: 25099678

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Project description:BackgroundStevens-Johnson syndrome (SJS) is an acute inflammatory vesiculobullous reaction of the skin and mucosa, often including the ocular surface, and toxic epidermal necrolysis (TEN) occurs with its progression. Although SJS/TEN is thought to be initiated by certain types of medication coupled with possible infection. In the present study we examined the multiplicative interaction(s) between HLA-A*0206 and 7 Toll-like receptor 3 (TLR3) Single-nucleotide polymorphisms (SNPs) in patients with SJS/TEN.Principal findingsWe analyzed the genotypes for HLA-A and 7 TLR3 SNPs in 110 Japanese SJS/TEN patients with severe ocular complications and 206 healthy volunteers to examine the interactions between the two loci. We found that HLA-A*0206 exhibited a high odds ratio for SJS/TEN (carrier frequency: OR = 5.1; gene frequency: OR = 4.0) and that there was a strong association with TLR3 rs.5743312T/T SNP (OR = 7.4), TLR3 rs.3775296T/T SNP (OR = 5.8), TLR3 rs.6822014G/G SNP (OR = 4.8), TLR3 rs.3775290A/A SNP (OR = 2.9), TLR3 rs.7668666A/A SNP (OR = 2.7), TLR3 rs.4861699G/G SNP (OR = 2.3), and TLR3 rs.11732384G/G SNP (OR = 1.9). There was strong linkage disequilibrium (LD) between rs.3775296 and rs.5743312 and between rs.7668666 and rs.3775290. The results of interaction analysis showed that the pair, HLA-A*0206 and TLR3 SNP rs3775296T/T, which exhibited strong LD with TLR3 rs.5743312, exerted more than additive effects (OR = 47.7). The other pairs, HLA-A*0206 and TLR3 rs.3775290A/A SNP (OR = 11.4) which was in strong LD with TLR3 rs7668666A/A SNP, and TLR3 rs4861699G/G SNP (OR = 7.6) revealed additive effects. Moreover, the combination HLA-A*0206 and TLR3 rs3775296T/T was stronger than the TLR3 rs6822014G/G and TLR3 rs3775290A/A pair, which reflected the interactions within the TLR3 gene alone.SignificanceBy interaction analysis, HLA-A*0206 and TLR3 SNP rs3775296T/T, which were in strong LD with TLR3 SNP rs5743312T/T, manifested more than additive effects that were stronger than the interactions within the TLR3 gene alone. Therefore, multiplicative interactions of HLA-A and TLR3 gene might be required for the onset of SJS/TEN with ocular complications.

Dataset Information

Trans-ethnic study confirmed independent associations of HLA-A02:06 and HLA-B44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications.

Publications

Trans-ethnic study confirmed independent associations of HLA-A02:06 and HLA-B44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications.

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Dataset Information

Trans-ethnic study confirmed independent associations of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications.

Publications

Trans-ethnic study confirmed independent associations of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Trans-ethnic study confirmed independent associations of HLA-A02:06 and HLA-B44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications.

Trans-ethnic study confirmed independent associations of HLA-A02:06 and HLA-B44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications.