Neuregulin 1 as a Potential Biomarker for Disease Progression in Moyamoya Disease: A Case-Control Study in Chinese Population.

OBJECTIVE: Moyamoya disease (MMD) is a rare and progressive stenosis of cerebral arteries characterized by abnormally proliferative vasculopathy. Current studies have demonstrated that Neuregulin 1 (NRG1) plays a key role in angiogenesis-related disorders. Thus, the aim of our study is to investigate the serum NRG1 levels and their clinical correlations in MMD patients.

METHODS: In this study, thirty adult patients with MMD and age-gender matched healthy controls were enrolled from our hospital between July 2020 and April 2022. Peripheral blood samples were collected at baseline, and clinical data were obtained from the electronic medical record system. Serum NRG1 concentrations were measured by enzyme-linked immunosorbent assay. Sanger sequencing was applied to detect the RNF213 p.R4810K mutation.

RESULTS: The serum NRG1 levels were significantly higher in MMD patients compared to controls (14.48±10.81 vs.7.54±6.35mmol/L, p<0.001). No statistical difference in baseline clinical characteristics was found between both groups. Correlation analyses showed that NRG1 levels were positively associated with Suzuki staging (r=0.4137, p=0.023) while not related to other clinical features (reduced cerebral blood flow, posterior cerebral artery involvement, bilateral or unilateral steno-occlusive changes). Furthermore, subgroup analysis revealed that MMD patients with the RNF213 p.R4810K mutation presented with significantly higher NRG1 levels than those without the mutation (9.60±0.929 vs. 25.89±4.338 mmol/L, p= 0.001).

CONCLUSIONS: Our study suggests that increased serum NRG1 levels may constitute a characteristic feature of MMD, indicating a potential positive correlation with disease progression and the presence of the RNF213 mutation. This positions NRG1 as a potentially crucial target for further studies aimed at comprehending the pathogenesis of MMD.