HLA-A*0206 with TLR3 Polymorphisms Exerts More than Additive Effects in Stevens-Johnson Syndrome with Severe Ocular Surface Complications
نویسندگان
چکیده
BACKGROUND Stevens-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 FINDINGS We 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. SIGNIFICANCE By 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.
منابع مشابه
HLA class I and II gene polymorphisms in Stevens-Johnson syndrome with ocular complications in Japanese
PURPOSE Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute-onset mucocutaneous diseases induced by infectious agents and/or inciting drugs. Although the pathobiological mechanisms underlying the onset of SJS/TEN have not been fully established, the extreme rarity of cutaneous and ocular surface reactions to drug therapies led us to suspect individual susceptibility. O...
متن کاملCold medicine-related Stevens–Johnson syndrome/toxic epidermal necrolysis with severe ocular complications–phenotypes and genetic predispositions
Stevens-Johnson syndrome (SJS) is an acute inflammatory vesiculobullous reaction of the skin and mucosa, such as the ocular surface, oral cavity, and genitals. In patients with extensive skin detachment and a poor prognosis, the condition is called toxic epidermal necrolysis (TEN). Severe ocular complications (SOCs) appear in some-but not all-SJS/TEN patients who are diagnosed by dermatologists...
متن کاملEthnic Differences in the Association Between Human Leukocyte Antigen and Stevens-Johnson Syndrome
The HLA-B12 antigen is significantly increased in Caucasian patients with Stevens-Johnson syndrome (SJS) with ocular complications, while HLA-A*0206 is strongly associated with Japanese patients with SJS/toxic epidermal necrolysis (TEN) with ocular complications. There are strong ethnic differences in the association between HLA and SJS/TEN. Regarding the association between HLA and drug-induce...
متن کاملHLA association with antipyretic analgesics-induced Stevens-Johnson Syndrome / toxic epidermal necrolysis with severe ocular surface complications in japanese patients
Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are severe adverse drug reactions which are very rare, acute, serious, and potentially fatal. They exhibit characteristic symptoms not only in the skin, but also in the mucosal tissues such as ocular surface, oral cavity, and genitals. Although antipyretic analgesics (AAs) are some of the most frequent causative dru...
متن کاملComparison of Complications and length of Hospitalization in management of Stevens-Johnson Syndrome with Systemic Steroid or Supportive Care
ABSTRACT Stevens-Johnson syndrome (SJS) is a serious acute self limited emergency in dermatology with considerable morbidity and mortality, Its specific therapy with systemic steroids has been the matter of challenge and controversy in the past 4 decades. The purpose of this study was comparing of complications and the length of hospitalization between those treated with steroids and supporti...
متن کامل