PMID- 28278336
OWN - NLM
STAT- MEDLINE
DCOM- 20170425
LR  - 20181113
IS  - 2168-6173 (Electronic)
IS  - 2168-6165 (Print)
IS  - 2168-6165 (Linking)
VI  - 135
IP  - 4
DP  - 2017 Apr 1
TI  - Human Leukocyte Antigen Class I Genes Associated With Stevens-Johnson Syndrome 
      and Severe Ocular Complications Following Use of Cold Medicine in a Brazilian 
      Population.
PG  - 355-360
LID - 10.1001/jamaophthalmol.2017.0074 [doi]
AB  - IMPORTANCE: Describing the association with human leukocyte antigen (HLA) alleles 
      could facilitate the understanding of increased risk factors for development of 
      Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients 
      with severe ocular complications (SOCs). OBJECTIVE: To investigate the 
      association between HLA class I genes and cold medicine (CM)-associated SJS/TEN 
      with SOCs. DESIGN, SETTING, AND PARTICIPANTS: This case-control study was 
      conducted between February 8, 2013, and August 29, 2014. Thirty-nine Brazilian 
      patients with CM-SJS/TEN of 74 patients with SJS/TEN with SOCs and 133 healthy 
      Brazilian volunteers were enrolled. Human leukocyte antigen class I genes (HLA-A, 
      HLA-B, and HLA-C) were examined to determine whether there was a genetic 
      predisposition for CM-SJS/TEN with SOC. Patients were interviewed to identify 
      possible etiologic factors. Data analysis was performed from April 14, 2013, to 
      August 29, 2014. MAIN OUTCOMES AND MEASURES: Genetic predisposition for 
      CM-SJS/TEN with SOCs by analysis of HLA class I genes. RESULTS: Of 74 patients 
      included in the analysis, 32 (43%) were male; mean (SD) age was 36.01 [15.42] 
      years. HLA-A*66:01 (odds ratio [OR], 24.0; 95% CI, 2.79-206.0; P < .001), 
      HLA-B*44:03 (OR, 2.71; 95% CI, 1.11-6.65; P = .04), and HLA-C*12:03 (OR, 5.6; 95% 
      CI, 1.67-18.80; P = .006) were associated with Brazilian CM-SJS/TEN with SOCs, 
      and HLA-A*11:01 (OR, 0.074; 95% CI, 0.004-1.26; P = .008), HLA-B*08:01 (OR, 0.15; 
      95% CI, 0.02-1.15; P = .048), and HLA-B*51:01 (OR, 0.23; 95% CI, 0.05-1.03; 
      P = .045) were inversely associated with Brazilian CM-SJS/TEN with SOCs (39 
      cases: 19 Pardo and 16 European ancestry; 14 males and 25 females; age, 35.2 
      [14.4] years; and 133 controls: 66 Pardo and 61 European ancestry; 55 males and 
      78 females; age, 41.2 [12.9] years). When multiple test correction within the HLA 
      locus, HLA-A*66:01 and HLA-C*12:03 demonstrated associations. When participants 
      were segregated into Pardo and locus is considered, HLA-A*66:01 was associated 
      with CM-SJS/TEN with SOC among individuals of both ethnic groups (Pardo: OR, 
      12.2; 95% CI, 1.19-125.0; P = .03; and European: OR, 21.2; 95% CI, 0.97-465.0; 
      P = .04). An association was observed only in the European cohort for HLA-B*44:03 
      (OR, 5.50; 95% CI, 1.47-20.50; P = .01) and HLA-C*12:03 (OR, 8.79; 95% CI, 
      1.83-42.20; P = .008). CONCLUSIONS AND RELEVANCE: This study suggests that 
      HLA-A*66:01 might be a marker for CM-SJS/TEN with SOCs in Brazilian individuals 
      of Pardo and European ancestry and that HLA-B*44:03 and HLA-C*12:03 might be 
      markers only in those of European ancestry. Moreover, HLA-A*11:01 might be a 
      marker of resistance to CM-SJS/TEN with SOCs.
FAU - Wakamatsu, Tais H
AU  - Wakamatsu TH
AD  - Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil.
FAU - Ueta, Mayumi
AU  - Ueta M
AD  - Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto, 
      Prefectural University of Medicine, Kyoto, Japan3Department of Human Genetics, 
      Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
FAU - Tokunaga, Katsushi
AU  - Tokunaga K
AD  - Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 
      Tokyo, Japan.
FAU - Okada, Yukinori
AU  - Okada Y
AD  - Department of Statistical Genetics, Osaka University, Osaka, Japan5Laboratory for 
      Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 
      Japan.
FAU - Loureiro, Renata R
AU  - Loureiro RR
AD  - Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil.
FAU - Costa, Karita A
AU  - Costa KA
AD  - Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil.
FAU - Sallum, Juliana Maria F
AU  - Sallum JMF
AD  - Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil.
FAU - Milhomens, Jose Arthur
AU  - Milhomens JA
AD  - Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil.
FAU - Inoue, Chikara
AU  - Inoue C
AD  - Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto, 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Sotozono, Chie
AU  - Sotozono C
AD  - Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, 
      Japan.
FAU - Gomes, Jose Alvaro P
AU  - Gomes JAP
AD  - Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil.
FAU - Kinoshita, Shigeru
AU  - Kinoshita S
AD  - Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto, 
      Prefectural University of Medicine, Kyoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - JAMA Ophthalmol
JT  - JAMA ophthalmology
JID - 101589539
RN  - 0 (Genetic Markers)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-C Antigens)
RN  - 0 (Multi-Ingredient Cold, Flu, and Allergy Medications)
SB  - IM
CIN - JAMA Ophthalmol. 2017 Apr 1;135(4):361-362. PMID: 28278317
CIN - JAMA Ophthalmol. 2017 Aug 1;135(8):894-895. PMID: 28715516
CIN - JAMA Ophthalmol. 2017 Aug 1;135(8):893-894. PMID: 28715524
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Brazil
MH  - Case-Control Studies
MH  - Child
MH  - Dry Eye Syndromes/chemically induced/*genetics
MH  - Female
MH  - Genetic Markers
MH  - Genotyping Techniques
MH  - HLA-A Antigens/*genetics
MH  - HLA-B Antigens/*genetics
MH  - HLA-C Antigens/*genetics
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multi-Ingredient Cold, Flu, and Allergy Medications/*adverse effects
MH  - Polymerase Chain Reaction
MH  - Stevens-Johnson Syndrome/etiology/*genetics
PMC - PMC5470496
COIS- Conflict of Interest Disclosures: All authors have completed and submitted the 
      ICMJE Form for Disclosure of Potential Conflicts of Interest and none were 
      reported.
EDAT- 2017/03/10 06:00
MHDA- 2017/04/26 06:00
PMCR- 2018/04/13
CRDT- 2017/03/10 06:00
PHST- 2017/03/10 06:00 [pubmed]
PHST- 2017/04/26 06:00 [medline]
PHST- 2017/03/10 06:00 [entrez]
PHST- 2018/04/13 00:00 [pmc-release]
AID - 2609103 [pii]
AID - eoi170007 [pii]
AID - 10.1001/jamaophthalmol.2017.0074 [doi]
PST - ppublish
SO  - JAMA Ophthalmol. 2017 Apr 1;135(4):355-360. doi: 
      10.1001/jamaophthalmol.2017.0074.