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Two Variants in the NOTCH4 and HLA-C Genes Contribute to Familial Clustering of Psoriasis

Psoriasis is a multifactorial immune-mediated skin disease with a strong genetic background. Previous studies reported that psoriasis with a family history (PFH) and sporadic psoriasis (SP) have a distinct manifestation and genetic predisposition. However, the genetic heterogeneity of PFH and SP in...

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Autores principales: Cai, Minglong, Huang, He, Hu, Zhulin, Yuan, Tao, Li, Weiran, Liu, Yaoguang, Zheng, Lijun, Zhang, Yan, Sheng, Yujun, Zhang, Xuejun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593743/
https://www.ncbi.nlm.nih.gov/pubmed/33134369
http://dx.doi.org/10.1155/2020/6907378
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author Cai, Minglong
Huang, He
Hu, Zhulin
Yuan, Tao
Li, Weiran
Liu, Yaoguang
Zheng, Lijun
Zhang, Yan
Sheng, Yujun
Zhang, Xuejun
author_facet Cai, Minglong
Huang, He
Hu, Zhulin
Yuan, Tao
Li, Weiran
Liu, Yaoguang
Zheng, Lijun
Zhang, Yan
Sheng, Yujun
Zhang, Xuejun
author_sort Cai, Minglong
collection PubMed
description Psoriasis is a multifactorial immune-mediated skin disease with a strong genetic background. Previous studies reported that psoriasis with a family history (PFH) and sporadic psoriasis (SP) have a distinct manifestation and genetic predisposition. However, the genetic heterogeneity of PFH and SP in the major histocompatibility complex (MHC) region has not been fully elucidated. To explore genetic variants in the MHC region that drive family aggregation of psoriasis, we included a total of 8,127 psoriasis cases and 9,906 healthy controls from Han Chinese and divided psoriasis into two subtypes, PFH (n = 1,538) and SP (n = 5,262). Then, we calculated the heritability of PFH and SP and performed a large-scale stratified association analysis. We confirmed that variants in the MHC region collectively explained a higher heritability of PFH (16.8%) than SP (13.3%). Further stratified association analysis illustrated that HLA-C∗06:02 and NOTCH4:G511S contribute to the family aggregation of psoriasis, and BTNL2:R281K specifically confers risk for SP. HLA-C∗06:02 and NOTCH4:G511S could partially explain why patients with PFH have a stronger genetic predisposition, more complex phenotypes, and more frequent other autoimmune diseases. The identification of the SP-specific variant BTNL2:R281K revealed that the genetic architecture of SP is not just a subset of PFH.
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spelling pubmed-75937432020-10-30 Two Variants in the NOTCH4 and HLA-C Genes Contribute to Familial Clustering of Psoriasis Cai, Minglong Huang, He Hu, Zhulin Yuan, Tao Li, Weiran Liu, Yaoguang Zheng, Lijun Zhang, Yan Sheng, Yujun Zhang, Xuejun Int J Genomics Research Article Psoriasis is a multifactorial immune-mediated skin disease with a strong genetic background. Previous studies reported that psoriasis with a family history (PFH) and sporadic psoriasis (SP) have a distinct manifestation and genetic predisposition. However, the genetic heterogeneity of PFH and SP in the major histocompatibility complex (MHC) region has not been fully elucidated. To explore genetic variants in the MHC region that drive family aggregation of psoriasis, we included a total of 8,127 psoriasis cases and 9,906 healthy controls from Han Chinese and divided psoriasis into two subtypes, PFH (n = 1,538) and SP (n = 5,262). Then, we calculated the heritability of PFH and SP and performed a large-scale stratified association analysis. We confirmed that variants in the MHC region collectively explained a higher heritability of PFH (16.8%) than SP (13.3%). Further stratified association analysis illustrated that HLA-C∗06:02 and NOTCH4:G511S contribute to the family aggregation of psoriasis, and BTNL2:R281K specifically confers risk for SP. HLA-C∗06:02 and NOTCH4:G511S could partially explain why patients with PFH have a stronger genetic predisposition, more complex phenotypes, and more frequent other autoimmune diseases. The identification of the SP-specific variant BTNL2:R281K revealed that the genetic architecture of SP is not just a subset of PFH. Hindawi 2020-10-19 /pmc/articles/PMC7593743/ /pubmed/33134369 http://dx.doi.org/10.1155/2020/6907378 Text en Copyright © 2020 Minglong Cai et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cai, Minglong
Huang, He
Hu, Zhulin
Yuan, Tao
Li, Weiran
Liu, Yaoguang
Zheng, Lijun
Zhang, Yan
Sheng, Yujun
Zhang, Xuejun
Two Variants in the NOTCH4 and HLA-C Genes Contribute to Familial Clustering of Psoriasis
title Two Variants in the NOTCH4 and HLA-C Genes Contribute to Familial Clustering of Psoriasis
title_full Two Variants in the NOTCH4 and HLA-C Genes Contribute to Familial Clustering of Psoriasis
title_fullStr Two Variants in the NOTCH4 and HLA-C Genes Contribute to Familial Clustering of Psoriasis
title_full_unstemmed Two Variants in the NOTCH4 and HLA-C Genes Contribute to Familial Clustering of Psoriasis
title_short Two Variants in the NOTCH4 and HLA-C Genes Contribute to Familial Clustering of Psoriasis
title_sort two variants in the notch4 and hla-c genes contribute to familial clustering of psoriasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593743/
https://www.ncbi.nlm.nih.gov/pubmed/33134369
http://dx.doi.org/10.1155/2020/6907378
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