RNF213 Variant and Infectious Burden Associated With Intracranial Artery Stenosis in Moyamoya Disease
Background The mechanisms driving the progression of moyamoya disease (MMD) remain unrecognized. There is evidence suggesting that genetic and environmental factors may be associated with intracranial artery stenosis. Here, we aimed to investigate the characteristics of infectious exposure and the a...
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| Language: | English |
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Wiley
2025-03-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.036830 |
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| _version_ | 1850155104171196416 |
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| author | Chaofan Zeng Peicong Ge Zihan Yin Junlin Lu Xiaofan Yu Junsheng Li Yuanren Zhai Chenglong Liu Qiheng He Wei Liu Jia Wang Xingju Liu Xun Ye Qian Zhang Rong Wang Yan Zhang Dong Zhang Jizong Zhao |
| author_facet | Chaofan Zeng Peicong Ge Zihan Yin Junlin Lu Xiaofan Yu Junsheng Li Yuanren Zhai Chenglong Liu Qiheng He Wei Liu Jia Wang Xingju Liu Xun Ye Qian Zhang Rong Wang Yan Zhang Dong Zhang Jizong Zhao |
| author_sort | Chaofan Zeng |
| collection | DOAJ |
| description | Background The mechanisms driving the progression of moyamoya disease (MMD) remain unrecognized. There is evidence suggesting that genetic and environmental factors may be associated with intracranial artery stenosis. Here, we aimed to investigate the characteristics of infectious exposure and the association of the RNF213 (RING finger protein 213) variant and infectious burden (IB) with intracranial artery stenosis of MMD. Methods and Results We prospectively recruited 275 patients with MMD. Participants underwent RNF213p.R4810K sequencing. Serum antibody titers of herpes simplex virus, cytomegalovirus, toxoplasma, rubella virus, and Epstein‐Barr virus were assessed and combined into an IB score. The degree of intracranial artery stenosis was measured by using the Willis narrowing score (WNS), which was then dichotomized as mild and severe. Multivariate regression analyses were performed to analyze variables associated with severe WNS. Patients with the RNF213 variant had a higher risk of severe WNS than wild‐type individuals (P=0.003). Patients with MMD with severe WNS showed an increased level of IB score (P<0.001). The RNF213 variant (odds ratio [OR], 2.832 [95% CI, 1.347–5.955]; P=0.006) and IB score (OR, 1.771 [95% CI, 1.286–2.439]; P<0.001) were significantly associated with severe WNS after adjusting for covariates. Furthermore, the associations between IB score and severe WNS were more prominent among patients with modifiable risk factors of elevated body mass index (Pinteraction<0.001), triglycerides (Pinteraction=0.011), and homocysteine (Pinteraction=0.016). Conclusions This study outlined a perspective of the genetic‐environmental interactions in the progression of MMD. The RNF213 variant and increased IB were associated with intracranial artery stenosis in MMD. The study will provide novel insights into the mechanism of disease progression, which may offer opportunities for early intervention of infectious exposure in MMD. |
| format | Article |
| id | doaj-art-4b182e9bcc4a4656a2ed983661967ad7 |
| institution | OA Journals |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-4b182e9bcc4a4656a2ed983661967ad72025-08-20T02:25:02ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-03-0114510.1161/JAHA.124.036830RNF213 Variant and Infectious Burden Associated With Intracranial Artery Stenosis in Moyamoya DiseaseChaofan Zeng0Peicong Ge1Zihan Yin2Junlin Lu3Xiaofan Yu4Junsheng Li5Yuanren Zhai6Chenglong Liu7Qiheng He8Wei Liu9Jia Wang10Xingju Liu11Xun Ye12Qian Zhang13Rong Wang14Yan Zhang15Dong Zhang16Jizong Zhao17Department of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery West China Hospital, Sichuan University Chengdu Sichuan ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaDepartment of Neurosurgery Beijing Tiantan Hospital, Capital Medical University Beijing ChinaBackground The mechanisms driving the progression of moyamoya disease (MMD) remain unrecognized. There is evidence suggesting that genetic and environmental factors may be associated with intracranial artery stenosis. Here, we aimed to investigate the characteristics of infectious exposure and the association of the RNF213 (RING finger protein 213) variant and infectious burden (IB) with intracranial artery stenosis of MMD. Methods and Results We prospectively recruited 275 patients with MMD. Participants underwent RNF213p.R4810K sequencing. Serum antibody titers of herpes simplex virus, cytomegalovirus, toxoplasma, rubella virus, and Epstein‐Barr virus were assessed and combined into an IB score. The degree of intracranial artery stenosis was measured by using the Willis narrowing score (WNS), which was then dichotomized as mild and severe. Multivariate regression analyses were performed to analyze variables associated with severe WNS. Patients with the RNF213 variant had a higher risk of severe WNS than wild‐type individuals (P=0.003). Patients with MMD with severe WNS showed an increased level of IB score (P<0.001). The RNF213 variant (odds ratio [OR], 2.832 [95% CI, 1.347–5.955]; P=0.006) and IB score (OR, 1.771 [95% CI, 1.286–2.439]; P<0.001) were significantly associated with severe WNS after adjusting for covariates. Furthermore, the associations between IB score and severe WNS were more prominent among patients with modifiable risk factors of elevated body mass index (Pinteraction<0.001), triglycerides (Pinteraction=0.011), and homocysteine (Pinteraction=0.016). Conclusions This study outlined a perspective of the genetic‐environmental interactions in the progression of MMD. The RNF213 variant and increased IB were associated with intracranial artery stenosis in MMD. The study will provide novel insights into the mechanism of disease progression, which may offer opportunities for early intervention of infectious exposure in MMD.https://www.ahajournals.org/doi/10.1161/JAHA.124.036830angiographyinfectious burdenintracranial artery stenosismoyamoya diseaseRNF213 |
| spellingShingle | Chaofan Zeng Peicong Ge Zihan Yin Junlin Lu Xiaofan Yu Junsheng Li Yuanren Zhai Chenglong Liu Qiheng He Wei Liu Jia Wang Xingju Liu Xun Ye Qian Zhang Rong Wang Yan Zhang Dong Zhang Jizong Zhao RNF213 Variant and Infectious Burden Associated With Intracranial Artery Stenosis in Moyamoya Disease Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease angiography infectious burden intracranial artery stenosis moyamoya disease RNF213 |
| title | RNF213 Variant and Infectious Burden Associated With Intracranial Artery Stenosis in Moyamoya Disease |
| title_full | RNF213 Variant and Infectious Burden Associated With Intracranial Artery Stenosis in Moyamoya Disease |
| title_fullStr | RNF213 Variant and Infectious Burden Associated With Intracranial Artery Stenosis in Moyamoya Disease |
| title_full_unstemmed | RNF213 Variant and Infectious Burden Associated With Intracranial Artery Stenosis in Moyamoya Disease |
| title_short | RNF213 Variant and Infectious Burden Associated With Intracranial Artery Stenosis in Moyamoya Disease |
| title_sort | rnf213 variant and infectious burden associated with intracranial artery stenosis in moyamoya disease |
| topic | angiography infectious burden intracranial artery stenosis moyamoya disease RNF213 |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.036830 |
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