Mapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing View Full Text


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Article Info

DATE

2021-02-11

AUTHORS

Yosuke Kawai, Yuki Hitomi, Mayumi Ueta, Seik-Soon Khor, Ken Nakatani, Chie Sotozono, Shigeru Kinoshita, Masao Nagasaki, Katsushi Tokunaga

ABSTRACT

Stevens–Johnson syndrome (SJS) and its severe condition with extensive skin detachment and a poor prognosis, toxic epidermal necrolysis (TEN), are immunologically mediated severe cutaneous reactions of the skin and mucous membranes such as the ocular surface. Genetic variations on the HLA-A and other autosomal genes have been identified as risk factors for cold medicine-related SJS/TEN with severe ocular complications (CM-SJS/TEN with SOC). Using a whole-genome sequencing (WGS) approach, we explored other susceptible variants of CM-SJS/TEN with SOC, especially among rare variants and structural variants (SVs). WGS was performed on samples from 133 patients with CM-SJS/TEN with SOC and 418 healthy controls to obtain single nucleotide polymorphisms (SNPs) and SVs. Genome-wide association tests were performed with these variants. Our genome-wide association test reproduced the associations of the common variants of HLA-A and loci on chromosome 16q12.1. We also identified novel associations of SVs on these loci and an aggregation of rare coding variants on the TPRM8 gene. In silico gene expression analysis on the HLA-A locus revealed that the SNP (rs12202296), which was significantly associated with susceptibility to CM-SJS/TEN with SOC, was correlated to an increase in HLA-A expression levels in the whole blood (P = 2.9 × 10−17), from the GTEx database. The majority of variants that were significantly associated with CM-SJS/TEN with SOC were found in non-coding regions, indicating the regulatory role of genetic variations in the pathogenesis of CM-SJS/TEN with SOC. More... »

PAGES

9

References to SciGraph publications

  • 2011-09-13. A whole-genome association study of major determinants for allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients in THE PHARMACOGENOMICS JOURNAL
  • 2013-05-29. The Genotype-Tissue Expression (GTEx) project in NATURE GENETICS
  • 2015-06-25. Japonica array: improved genotype imputation by designing a population-specific SNP array with 1070 Japanese individuals in JOURNAL OF HUMAN GENETICS
  • 2014-04-30. Independent strong association of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe mucosal involvement in SCIENTIFIC REPORTS
  • 2019-11-07. Identification of HLA-A*02:06:01 as the primary disease susceptibility HLA allele in cold medicine-related Stevens-Johnson syndrome with severe ocular complications by high-resolution NGS-based HLA typing in SCIENTIFIC REPORTS
  • 2015-08-10. SpeedSeq: ultra-fast personal genome analysis and interpretation in NATURE METHODS
  • 2017-01-19. Genome-wide association study using the ethnicity-specific Japonica array: identification of new susceptibility loci for cold medicine-related Stevens–Johnson syndrome with severe ocular complications in JOURNAL OF HUMAN GENETICS
  • 2006-06-20. BRD2 is one of BRD7-interacting proteins and its over-expression could initiate apoptosis in MOLECULAR AND CELLULAR BIOCHEMISTRY
  • 2004-04. A marker for Stevens–Johnson syndrome in NATURE
  • 2017-04-24. Genome-wide profiling of heritable and de novo STR variations in NATURE METHODS
  • 2015-09-30. An integrated map of structural variation in 2,504 human genomes in NATURE
  • 2017-04-03. The impact of structural variation on human gene expression in NATURE GENETICS
  • 2007-04-26. BRD7 suppresses the growth of Nasopharyngeal Carcinoma cells (HNE1) through negatively regulating β-catenin and ERK pathways in MOLECULAR AND CELLULAR BIOCHEMISTRY
  • 2015-02-25. Second-generation PLINK: rising to the challenge of larger and richer datasets in GIGASCIENCE
  • 2015-09-25. Integrating ChIP-sequencing and digital gene expression profiling to identify BRD7 downstream genes and construct their regulating network in MOLECULAR AND CELLULAR BIOCHEMISTRY
  • 2014-06-26. LUMPY: a probabilistic framework for structural variant discovery in GENOME BIOLOGY
  • 2016-07-04. BRD7 plays an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway in CELLULAR & MOLECULAR IMMUNOLOGY
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    23 schema:description Stevens–Johnson syndrome (SJS) and its severe condition with extensive skin detachment and a poor prognosis, toxic epidermal necrolysis (TEN), are immunologically mediated severe cutaneous reactions of the skin and mucous membranes such as the ocular surface. Genetic variations on the HLA-A and other autosomal genes have been identified as risk factors for cold medicine-related SJS/TEN with severe ocular complications (CM-SJS/TEN with SOC). Using a whole-genome sequencing (WGS) approach, we explored other susceptible variants of CM-SJS/TEN with SOC, especially among rare variants and structural variants (SVs). WGS was performed on samples from 133 patients with CM-SJS/TEN with SOC and 418 healthy controls to obtain single nucleotide polymorphisms (SNPs) and SVs. Genome-wide association tests were performed with these variants. Our genome-wide association test reproduced the associations of the common variants of HLA-A and loci on chromosome 16q12.1. We also identified novel associations of SVs on these loci and an aggregation of rare coding variants on the TPRM8 gene. In silico gene expression analysis on the HLA-A locus revealed that the SNP (rs12202296), which was significantly associated with susceptibility to CM-SJS/TEN with SOC, was correlated to an increase in HLA-A expression levels in the whole blood (P = 2.9 × 10−17), from the GTEx database. The majority of variants that were significantly associated with CM-SJS/TEN with SOC were found in non-coding regions, indicating the regulatory role of genetic variations in the pathogenesis of CM-SJS/TEN with SOC.
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    29 schema:keywords Association Test
    30 CM-SJS/TEN
    31 GTEx database
    32 HLA
    33 HLA-A locus
    34 SJS/toxic epidermal necrolysis
    35 SOC
    36 Stevens-Johnson syndrome
    37 WGS
    38 aggregation
    39 analysis
    40 approach
    41 association
    42 autosomal genes
    43 blood
    44 chromosome 16q12.1
    45 cold medicine-related SJS/TEN
    46 cold medicine-related Stevens-Johnson syndrome
    47 common variants
    48 complications
    49 conditions
    50 control
    51 cutaneous reactions
    52 database
    53 detachment
    54 epidermal necrolysis
    55 expression analysis
    56 expression levels
    57 extensive skin detachment
    58 factors
    59 gene expression analysis
    60 genes
    61 genetic variation
    62 genome-wide association tests
    63 healthy controls
    64 increase
    65 levels
    66 loci
    67 majority
    68 majority of variants
    69 mapping
    70 membrane
    71 mucous membranes
    72 necrolysis
    73 non-coding regions
    74 novel associations
    75 nucleotide polymorphisms
    76 ocular complications
    77 ocular surface
    78 pathogenesis
    79 patients
    80 polymorphism
    81 poor prognosis
    82 prognosis
    83 rare variants
    84 reaction
    85 region
    86 regulatory role
    87 resequencing
    88 risk factors
    89 role
    90 samples
    91 sequencing approach
    92 severe conditions
    93 severe cutaneous reactions
    94 severe ocular complications
    95 silico gene expression analysis
    96 single nucleotide polymorphisms
    97 skin
    98 skin detachment
    99 structural variants
    100 surface
    101 susceptibility
    102 susceptible variants
    103 syndrome
    104 test
    105 toxic epidermal necrolysis
    106 variants
    107 variation
    108 whole blood
    109 whole genome sequencing approach
    110 whole-genome resequencing
    111 wide association test
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