Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct 28:6:50.
doi: 10.1038/s41439-019-0082-6. eCollection 2019.

Association of HLA class I and II gene polymorphisms with acetaminophen-related Stevens-Johnson syndrome with severe ocular complications in Japanese individuals

Mayumi Ueta  1 , Ryosuke Nakamura  2 , Yoshiro Saito  2 , Katsushi Tokunaga  3   4 , Chie Sotozono  5 , Toshio Yabe  6 , Michiko Aihara  7 , Kayoko Matsunaga  8 , Shigeru Kinoshita  1
Affiliations

Association of HLA class I and II gene polymorphisms with acetaminophen-related Stevens-Johnson syndrome with severe ocular complications in Japanese individuals

Mayumi Ueta et al. Hum Genome Var. .

Abstract

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute-onset mucocutaneous diseases induced by infectious agents and/or inciting drugs. We have reported that the main causative drugs for SJS/TEN with severe ocular complications (SOC) were cold medicines, including multi-ingredient cold medications and nonsteroidal anti-inflammatory drugs (NSAIDs). Moreover, we also reported that acetaminophen is the most frequent causative drug in various cold medicines. In this study, we focused on acetaminophen-related SJS/TEN with SOC and analyzed HLA-class II (HLA-DRB1, DQB1) in addition to HLA-class I (HLA-A, B, C). We studied the histocompatibility antigen genes HLA-DRB1 and DQB1 in addition to HLA-A, B, and C in 80 Japanese patients with acetaminophen-related SJS/TEN with SOC. We performed polymerase chain reaction amplification followed by hybridization with sequence-specific oligonucleotide probes (PCR-SSO) using commercial bead-based typing kits. We also used genotyped data from 113 healthy volunteers for HLA-DRB1 and DQB1, and 639 healthy volunteers for HLA-A, B, and C. HLA-DRB1*08:03 and DRB1*12:02 were associated with acetaminophen-related SJS/TEN with SOC, although the results ceased to be significant when we corrected the p-value for the number of alleles detected. HLA-A*02:06 was strongly associated with acetaminophen-related SJS/TEN with SOC (carrier frequency: p = 4.7 × 10-12, Pc = 6.6 × 10-11, OR = 6.0; gene frequency: p = 8.0 × 10-13, Pc = 1.1 × 10-11, OR = 4.9). HLA-B*13:01 (carrier frequency: p = 2.0 × 10-3, Pc = 0.042, OR = 4.1; gene frequency: p = 2.2 × 10-3, Pc = 0.047, OR = 3.9), HLA-B*44:03 (carrier frequency: p = 2.1 × 10-3, Pc = 0.045, OR = 2.4) and HLA-C*14:03 (carrier frequency: p = 3.4 × 10-3, Pc = 0.045, OR = 2.3) were also significantly associated, while HLA-A*24:02 was inversely associated (gene frequency: p = 6.3 × 10-4, Pc = 8.8 × 10-3, OR = 0.5). Acetaminophen-related SJS/TEN with SOC was not associated with HLA-class II (HLA-DRB1, DQB1). However, for acetaminophen-related SJS/TEN with SOC, we found an association with HLA-B*13:01 and HLA- C*14:03 in addition to HLA-A*02:06 and HLA-B*44:03, which have been described previously.

Keywords: Immunological disorders; Predictive markers.

PubMed Disclaimer

Conflict of interest statement

Conflict of interestThe authors declare that they have no conflict of interest.

References

    1. Sotozono C, et al. Predictive factors associated with acute ocular involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis. Am. J. Ophthalmol. 2015;160:228–237 e2. doi: 10.1016/j.ajo.2015.05.002. - DOI - PubMed
    1. Power WJ, Ghoraishi M, Merayo-Lloves J, Neves RA, Foster CS. Analysis of the acute ophthalmic manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum. Ophthalmology. 1995;102:1669–1676. doi: 10.1016/S0161-6420(95)30811-1. - DOI - PubMed
    1. Yamane Y, Aihara M, Ikezawa Z. Analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan from 2000 to 2006. Allergol. Int. 2007;56:419–425. doi: 10.2332/allergolint.O-07-483. - DOI - PubMed
    1. Ueta M, et al. Association between prostaglandin E receptor 3 polymorphisms and Stevens-Johnson syndrome identified by means of a genome-wide association study. J. Allergy Clin. Immunol. 2010;126:1218–1225 e10. doi: 10.1016/j.jaci.2010.08.007. - DOI - PubMed
    1. Ueta M, Kinoshita S. Ocular surface inflammation is regulated by innate immunity. Prog. Retin. Eye Res. 2012;31:551–575. doi: 10.1016/j.preteyeres.2012.05.003. - DOI - PubMed