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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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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. |
format | Online Article Text |
id | pubmed-7593743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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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