BackgroundThe pathogenic mechanism of brain arteriovenous malformation (bAVM) is poorly understood. A growing body of evidence indicates that genetic factors play crucial roles in bAVM. This study examined genetic variants associated with bAVM through quantitative synthesis and qualitative description of literature.MethodsFive databases were searched to gather potentially relevant articles published up to January 2022. STATA 14.0 software was used for statistical analyses. Pooled odds ratios and 95% confidence intervals were calculated with random effect models, and heterogeneity was assessed using the Cochran Q test and quantified with the I2 test. Sensitivity and publication bias were analyzed to test the robustness of the associations. Variants identified in only one study or with great heterogeneity were not suitable for pooling association analysis, and therefore a qualitative systematic review was performed.ResultsIn total, 30 papers were included in a systematic review involving 4709 cases and 7832 controls, where 17 papers were in a meta-analysis. A suggested association of bAVM was observed with ACVRL1 rs2071219 in the additive model and CDKN2B-AS1 rs1333040 in the recessive and additive models. Other variants of genes that could not be analyzed were summarized by qualitative description. These genes were mostly involved in bone morphogenic protein/transforming growth factor beta (BMP/TGF-β), vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR), and RAS-mitogen activated protein kinase (MAPK) signaling and inflammation.ConclusionsAccording to our meta-analysis, ACVRL1 rs2071219 and CDKN2B-AS1 rs1333040 were potentially associated with bAVM. Multiple pathological signaling pathways could affect disease development. Future studies should aim to determine the interaction of candidate genes with environmental risk factors and to elucidate detailed mechanisms of action of variants and genes.1
Purpose Genome-wide association studies (GWAS) have revealed that common variants on or near EDNRA , HDAC9 , SOX17 , RP1 , CDKN2B-AS1 , and RBBP8 genes are associated with intracranial aneurysm (IA) in European or Japanese populations. However, due to population heterogeneity, whether these loci are associated with IA pathogenesis in Chinese individuals is still unknown. The purpose of this study was to investigate associations among GWAS-identified loci and risk of IA in a Chinese population. Materials and Methods A total of 765 individuals (including 230 IA patients and 535 controls) were involved in this study. Twelve single nucleotide polymorphisms (SNPs) of candidate loci were genotyped using the Sequenom MassARRAY platform. Associations were analyzed using univariate or multivariate logistic regression analysis. Results SNPs in CDKN2B-AS1 (especially rs10757272) showed significant associations with IA in dominant and additive models [odds ratio (OR), 2.99 and 1.43; 95% confidence interval (CI), 1.44–6.24 and 1.10–1.86, respectively]. A SNP near HDAC9 (rs10230207) was associated with IA in the dominant model (OR, 1.42; 95% CI, 1.01–1.99). One SNP near RP1 (rs1072737) showed a protective effect on IA in the dominant model (OR, 0.66; 95% CI, 0.46–0.95), while another SNP in RP1 (rs9298506) showed a risk effect on IA in a recessive model (OR, 3.82; 95% CI, 1.84–7.91). No associations were observed among common variants near EDNRA , SOX17 , or RBBP8 and IA. Conclusion These data partially confirmed earlier results and showed that variants in CDKN2B-AS1 , RP1 , and HDAC9 could be genetic susceptibility factors for IA in a Chinese population.
BackgroundThis study aimed to assess whether pregnancy and puerperium were associated with the risk of brain arteriovenous malformation (bAVM) haemorrhage.MethodsA retrospective review was conducted in Xiangya Hospital, Central South University from January 2012 to December 2021. A case–crossover design was adopted to calculate the incidence density of bAVM-related haemorrhage among female patients in risk (pregnancy and puerperium) and control (non-pregnancy and non-puerperium) periods, according to four scenarios observed in different populations (scenario I: patients with haemorrhagic bAVM of all ages; scenario II: patients with haemorrhagic bAVM of all ages, with at least one previous pregnancy; scenario III: patients with haemorrhagic bAVM who are of reproductive age (15–45 years); scenario IV: patients with haemorrhagic bAVM of reproductive age (15–45 years), with at least one previous pregnancy. Next, a comprehensive literature aggregation (up to April 2022) was performed for evidence synthesis.ResultsAmong the 311 female patients with haemorrhagic bAVM, a significant haemorrhage risk during pregnancy and puerperium was found in Scenarios I (relative risk [RR], 2.08; 95% CI, 1.28 to 3.39), II (RR, 3.21; 95% CI, 1.95 to 5.31) and IV (RR, 2.92; 95% CI, 1.73 to 4.93); however, a suggestive risk was found in scenario III (RR, 1.62; 95% CI, 0.99 to 2.67). Evidence synthesis revealed a consistent haemorrhage risk among patients of all ages (RR, 3.15; 95% CI, 1.93 to 5.15) and those of reproductive age (RR, 1.29; 95% CI, 0.89 to 1.86).ConclusionCompared with most previous studies, a higher but relatively moderate risk for bAVM-related haemorrhage was identified during pregnancy and puerperium. Individualised prevention and treatment strategies should be preferred when neurosurgeons make clinical decisions.
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