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Amplified Risk of Intracranial Artery Stenosis/Occlusion Associated With RNF213 p.R4810K in Familial Hypercholesterolemia
BACKGROUND: The RNF213 p.R4810K variant is associated with moyamoya disease in East Asian individuals and increases the risk of developing intracranial major artery stenosis/occlusion (ICASO) that affects anterior circulation. Meanwhile, 0.5% to 2.5% of asymptomatic East Asian individuals also carry...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442882/ https://www.ncbi.nlm.nih.gov/pubmed/37614551 http://dx.doi.org/10.1016/j.jacasi.2023.03.011 |
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author | Noda, Kotaro Hattori, Yorito Hori, Mika Nakaoku, Yuriko Tanaka, Akito Yoshimoto, Takeshi Nishimura, Kunihiro Yokota, Takanori Harada-Shiba, Mariko Ihara, Masafumi |
author_facet | Noda, Kotaro Hattori, Yorito Hori, Mika Nakaoku, Yuriko Tanaka, Akito Yoshimoto, Takeshi Nishimura, Kunihiro Yokota, Takanori Harada-Shiba, Mariko Ihara, Masafumi |
author_sort | Noda, Kotaro |
collection | PubMed |
description | BACKGROUND: The RNF213 p.R4810K variant is associated with moyamoya disease in East Asian individuals and increases the risk of developing intracranial major artery stenosis/occlusion (ICASO) that affects anterior circulation. Meanwhile, 0.5% to 2.5% of asymptomatic East Asian individuals also carry this variant. As such, additional factors are likely required to develop ICASO in variant carriers. Familial hypercholesterolemia (FH) is a common genetic disorder in Japan that has a significant associated risk of developing premature coronary atherosclerosis; however, the relationship between ICASO and FH remains unknown. OBJECTIVES: This study aimed to determine if FH facilitates RNF213 p.R4810K carriers to develop ICASO. METHODS: We enrolled patients with FH who had undergone brain magnetic resonance angiography at our hospital from May 2005 to March 2020. The RNF213 p.R4810K variant, and LDLR and PCSK9 mutations were genotyped. ICASO lesions in the brain magnetic resonance angiogram were analyzed. RESULTS: Six RNF213 p.R4810K variant carriers were identified among 167 patients with FH (LDLR, n = 104; PCSK9, n = 22). Five of the carriers (83.3%) exhibited ICASO in the anterior circulation; a significant difference in ICASO frequency was observed between the variant carriers and noncarriers (P = 0.025). The median number of stenotic or occluded arteries in the anterior circulation was also significantly larger in the variant carriers (3 vs 1, P = 0.01); however, did not differ between patients with FH with LDLR and PCSK9 mutations. CONCLUSIONS: Patients with FH exhibit increased prevalence and severity of ICASO associated with RNF213 p.R4810K. Gene mutations for FH may confer an increased risk of ICASO in RNF213 p.R4810K carriers. |
format | Online Article Text |
id | pubmed-10442882 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-104428822023-08-23 Amplified Risk of Intracranial Artery Stenosis/Occlusion Associated With RNF213 p.R4810K in Familial Hypercholesterolemia Noda, Kotaro Hattori, Yorito Hori, Mika Nakaoku, Yuriko Tanaka, Akito Yoshimoto, Takeshi Nishimura, Kunihiro Yokota, Takanori Harada-Shiba, Mariko Ihara, Masafumi JACC Asia Original Research BACKGROUND: The RNF213 p.R4810K variant is associated with moyamoya disease in East Asian individuals and increases the risk of developing intracranial major artery stenosis/occlusion (ICASO) that affects anterior circulation. Meanwhile, 0.5% to 2.5% of asymptomatic East Asian individuals also carry this variant. As such, additional factors are likely required to develop ICASO in variant carriers. Familial hypercholesterolemia (FH) is a common genetic disorder in Japan that has a significant associated risk of developing premature coronary atherosclerosis; however, the relationship between ICASO and FH remains unknown. OBJECTIVES: This study aimed to determine if FH facilitates RNF213 p.R4810K carriers to develop ICASO. METHODS: We enrolled patients with FH who had undergone brain magnetic resonance angiography at our hospital from May 2005 to March 2020. The RNF213 p.R4810K variant, and LDLR and PCSK9 mutations were genotyped. ICASO lesions in the brain magnetic resonance angiogram were analyzed. RESULTS: Six RNF213 p.R4810K variant carriers were identified among 167 patients with FH (LDLR, n = 104; PCSK9, n = 22). Five of the carriers (83.3%) exhibited ICASO in the anterior circulation; a significant difference in ICASO frequency was observed between the variant carriers and noncarriers (P = 0.025). The median number of stenotic or occluded arteries in the anterior circulation was also significantly larger in the variant carriers (3 vs 1, P = 0.01); however, did not differ between patients with FH with LDLR and PCSK9 mutations. CONCLUSIONS: Patients with FH exhibit increased prevalence and severity of ICASO associated with RNF213 p.R4810K. Gene mutations for FH may confer an increased risk of ICASO in RNF213 p.R4810K carriers. Elsevier 2023-06-13 /pmc/articles/PMC10442882/ /pubmed/37614551 http://dx.doi.org/10.1016/j.jacasi.2023.03.011 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Noda, Kotaro Hattori, Yorito Hori, Mika Nakaoku, Yuriko Tanaka, Akito Yoshimoto, Takeshi Nishimura, Kunihiro Yokota, Takanori Harada-Shiba, Mariko Ihara, Masafumi Amplified Risk of Intracranial Artery Stenosis/Occlusion Associated With RNF213 p.R4810K in Familial Hypercholesterolemia |
title | Amplified Risk of Intracranial Artery Stenosis/Occlusion Associated With RNF213 p.R4810K in Familial Hypercholesterolemia |
title_full | Amplified Risk of Intracranial Artery Stenosis/Occlusion Associated With RNF213 p.R4810K in Familial Hypercholesterolemia |
title_fullStr | Amplified Risk of Intracranial Artery Stenosis/Occlusion Associated With RNF213 p.R4810K in Familial Hypercholesterolemia |
title_full_unstemmed | Amplified Risk of Intracranial Artery Stenosis/Occlusion Associated With RNF213 p.R4810K in Familial Hypercholesterolemia |
title_short | Amplified Risk of Intracranial Artery Stenosis/Occlusion Associated With RNF213 p.R4810K in Familial Hypercholesterolemia |
title_sort | amplified risk of intracranial artery stenosis/occlusion associated with rnf213 p.r4810k in familial hypercholesterolemia |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442882/ https://www.ncbi.nlm.nih.gov/pubmed/37614551 http://dx.doi.org/10.1016/j.jacasi.2023.03.011 |
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