Genetic variants in the HLA region contribute to the risk of cerebral palsy
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
Cerebral palsy (CP) is the most common physical disability in childhood, and genetic factors play an important role in its pathogenesis. However, the genetic contributions remain incompletely elucidated. Here, we conducted a two-stage association study between 1090 CP cases and 1100 healthy controls after whole exome sequencing. The human leukocyte antigen (HLA) allelic predispositions were further analyzed in overall CP and subgroups using multivariate logistic regression. We found a strong signal in the HLA region on chromosome 6, where rs3131787 harbored the most significant association with CP (P = 2.05 × 10-14, OR = 2.22). In comparison to controls, the carrier frequencies of HLA-B*13:02 were significantly higher in children with CP (9.82 % in control vs 19.27 % in CP, P = 1.03 × 10-4, OR = 2.17). Furthermore, the effect of HLA-B*13:02 on increasing the risk of CP mainly existed in cryptogenic CP without exposure to premature birth, low birth weight, birth asphyxia, or periventricular leukomalacia. This study indicated a strong association of HLA variants with CP, which implied that immune dysregulation resulting from immunogenetic variants might underlie the pathogenesis of CP. Our findings provide genetic evidence that an immunomodulator may serve as a promising therapeutic intervention for patients with CP by reinstating the neuroinflammation hemostasis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1870 |
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| Enthalten in: |
Biochimica et biophysica acta. Molecular basis of disease - 1870(2024), 3 vom: 01. Feb., Seite 167008 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cheng, Ye [VerfasserIn] |
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| Links: |
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| Themen: |
Cerebral palsy |
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| Anmerkungen: |
Date Completed 20.02.2024 Date Revised 27.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbadis.2023.167008 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366540866 |
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| 245 | 1 | 0 | |a Genetic variants in the HLA region contribute to the risk of cerebral palsy |
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| 520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Cerebral palsy (CP) is the most common physical disability in childhood, and genetic factors play an important role in its pathogenesis. However, the genetic contributions remain incompletely elucidated. Here, we conducted a two-stage association study between 1090 CP cases and 1100 healthy controls after whole exome sequencing. The human leukocyte antigen (HLA) allelic predispositions were further analyzed in overall CP and subgroups using multivariate logistic regression. We found a strong signal in the HLA region on chromosome 6, where rs3131787 harbored the most significant association with CP (P = 2.05 × 10-14, OR = 2.22). In comparison to controls, the carrier frequencies of HLA-B*13:02 were significantly higher in children with CP (9.82 % in control vs 19.27 % in CP, P = 1.03 × 10-4, OR = 2.17). Furthermore, the effect of HLA-B*13:02 on increasing the risk of CP mainly existed in cryptogenic CP without exposure to premature birth, low birth weight, birth asphyxia, or periventricular leukomalacia. This study indicated a strong association of HLA variants with CP, which implied that immune dysregulation resulting from immunogenetic variants might underlie the pathogenesis of CP. Our findings provide genetic evidence that an immunomodulator may serve as a promising therapeutic intervention for patients with CP by reinstating the neuroinflammation hemostasis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cerebral palsy | |
| 650 | 4 | |a GWAS | |
| 650 | 4 | |a Genetics | |
| 650 | 4 | |a HLA | |
| 650 | 4 | |a Immunogenetics | |
| 650 | 7 | |a HLA-B Antigens |2 NLM | |
| 700 | 1 | |a Xu, Yiran |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hongwei |e verfasserin |4 aut | |
| 700 | 1 | |a Qiao, Yimeng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yangong |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Lili |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Changlian |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, Qinghe |e verfasserin |4 aut | |
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