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

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yosuke Kawai, Yuki Hitomi, Mayumi Ueta, Seik-Soon Khor, Ken Nakatani, Chie Sotozono, Shigeru Kinoshita, Masao Nagasaki, Katsushi Tokunaga
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/27bec4b4ac454684b32bc1932294c468
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:27bec4b4ac454684b32bc1932294c468
record_format	dspace
spelling	oai:doaj.org-article:27bec4b4ac454684b32bc1932294c4682021-12-02T14:27:03ZMapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing10.1038/s41525-021-00171-22056-7944https://doaj.org/article/27bec4b4ac454684b32bc1932294c4682021-02-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00171-2https://doaj.org/toc/2056-7944Abstract 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.Yosuke KawaiYuki HitomiMayumi UetaSeik-Soon KhorKen NakataniChie SotozonoShigeru KinoshitaMasao NagasakiKatsushi TokunagaNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Yosuke Kawai Yuki Hitomi Mayumi Ueta Seik-Soon Khor Ken Nakatani Chie Sotozono Shigeru Kinoshita Masao Nagasaki Katsushi Tokunaga Mapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing
description	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.
format	article
author	Yosuke Kawai Yuki Hitomi Mayumi Ueta Seik-Soon Khor Ken Nakatani Chie Sotozono Shigeru Kinoshita Masao Nagasaki Katsushi Tokunaga
author_facet	Yosuke Kawai Yuki Hitomi Mayumi Ueta Seik-Soon Khor Ken Nakatani Chie Sotozono Shigeru Kinoshita Masao Nagasaki Katsushi Tokunaga
author_sort	Yosuke Kawai
title	Mapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing
title_short	Mapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing
title_full	Mapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing
title_fullStr	Mapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing
title_full_unstemmed	Mapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing
title_sort	mapping of susceptible variants for cold medicine-related stevens–johnson syndrome by whole-genome resequencing
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/27bec4b4ac454684b32bc1932294c468
work_keys_str_mv	AT yosukekawai mappingofsusceptiblevariantsforcoldmedicinerelatedstevensjohnsonsyndromebywholegenomeresequencing AT yukihitomi mappingofsusceptiblevariantsforcoldmedicinerelatedstevensjohnsonsyndromebywholegenomeresequencing AT mayumiueta mappingofsusceptiblevariantsforcoldmedicinerelatedstevensjohnsonsyndromebywholegenomeresequencing AT seiksoonkhor mappingofsusceptiblevariantsforcoldmedicinerelatedstevensjohnsonsyndromebywholegenomeresequencing AT kennakatani mappingofsusceptiblevariantsforcoldmedicinerelatedstevensjohnsonsyndromebywholegenomeresequencing AT chiesotozono mappingofsusceptiblevariantsforcoldmedicinerelatedstevensjohnsonsyndromebywholegenomeresequencing AT shigerukinoshita mappingofsusceptiblevariantsforcoldmedicinerelatedstevensjohnsonsyndromebywholegenomeresequencing AT masaonagasaki mappingofsusceptiblevariantsforcoldmedicinerelatedstevensjohnsonsyndromebywholegenomeresequencing AT katsushitokunaga mappingofsusceptiblevariantsforcoldmedicinerelatedstevensjohnsonsyndromebywholegenomeresequencing
_version_	1718391298658926592

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

Ejemplares similares