Association between RNF213 c.14576G>A Variant (rs112735431) and Peripheral Pulmonary Artery Stenosis in Moyamoya Disease.
Association between RNF213 c.14576G>A Variant (rs112735431) and Peripheral Pulmonary Artery Stenosis in Moyamoya Disease.
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RNF213 c.14576G>A 变异 (rs112735431) 与烟雾病中的外周肺动脉狭窄之间的关联。
DOI：
10.1159/000519717
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发表时间：
2021
影响因子：
2.9
通讯作者：
Tominaga Teiji
中科院分区：
文献类型：
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作者：
Ozaki Dan;Endo Hidenori;Tashiro Ryosuke;Sugimura Koichiro;Tatebe Shunsuke;Yasuda Satoshi;Tomata Yasutake;Endo Toshiki;Tominaga Keita;Niizuma Kuniyasu;Fujimura Miki;Tominaga Teiji
背景烟雾病（Moyamoya disease，MMD）和外周肺动脉狭窄（peripheral pulmonary artery stenosis，PPAS）是一种少见的疾病，表现为不同器官的狭窄闭塞性血管病变。遗传学研究确定了RNF 213多态性c。14576 G> A（rs 112735431）作为东亚MMD的易感性变体。RNF 213多态性c. 14576 G> A还与其他器官的各种血管病变有关。本研究旨在明确PPAS在MMD患者中的发病率和临床表现，并分析RNF 213基因型与PPAS的相关性。方法采用回顾性病例对照研究方法，对306例MMD/准MMD患者的RNF 213基因多态性与PPAS的相关性进行研究，方法回顾性分析2015年1月至2020年12月收治的MMD患者的病历和影像学资料。结果3例MMD/准MMD患者出现PPAS（0.98%，3/306）。RNF 213多态性c.对306例MMD/准MMD患者进行了14576 G> A测定。RNF 213-野生型、RNF 213-杂合子和RNF 213-纯合子MMD/准MMD患者的PPAS发生率分别为0%（0/101）、0.5%（1/200）和40%（2/5）。PPAS与RNF 213 c纯合子多态性的相关性研究14576 G> A在MMD/准MMD患者中具有统计学显著性（p= 0.0018）。在所有病例中，PPAS所致的肺动脉高压在儿童期和青少年期明显。1例患者因严重心肺功能障碍而放弃手术指征。14576 G> A可能是MMD/准MMD患者PPAS的潜在易感因素。尽管PPAS相对罕见，但应注意确定MMD/准MMD患者的手术适应症。
BackgroundMoyamoya disease (MMD) and peripheral pulmonary artery stenosis (PPAS) are relatively rare and demonstrate steno-occlusive vascular lesions in different organs. Genetic studies identified RNF213 polymorphism c. 14576G> A (rs112735431) as a susceptibility variant for East Asian MMD. RNF213 polymorphism c. 14576G> A is further associated with various vascular lesions of other organs. In this study, we aimed to clarify the incidence and clinical manifestations of PPAS in MMD patients and analyze the correlation between RNF213 genotype and PPAS.MethodsThis retrospective case-control study investigated the association between RNF213 polymorphism and PPAS in 306 MMD/quasi-MMD patients, reviewing the medical charts and imaging records of consecutive patients with MMD admitted from January 2015 to December 2020.ResultsPPAS was observed in 3 MMD/quasi-MMD patients (0.98%, 3/306). RNF213 polymorphism c. 14576G> A was determined for all 306 MMD/quasi-MMD patients. The incidence of PPAS in RNF213-wildtype, RNF213-heterozygote, and RNF213-homozygote MMD/quasi-MMD patients was 0%(0/101), 0.5%(1/200), and 40%(2/5), respectively. The association between PPAS and homozygote polymorphism of RNF213 c. 14576G> A was statistically significant in MMD/quasi-MMD patients (p= 0.0018). In all cases, pulmonary artery hypertension due to PPAS was evident during their childhood and young adolescent stages. Surgical indications for MMD were discouraged in 1 case due to her severe cardiopulmonary dysfunction.ConclusionsThe homozygote variant of RNF213 polymorphism c. 14576G> A can be a potential predisposing factor for PPAS in MMD/quasi-MMD patients. Despite the relatively rare entity, PPAS should be noted to determine surgical indications for MMD/quasi-MMD patients.