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Associations of Reported Genetic Risk Loci with Sporadic Brain Arteriovenous Malformations: Meta-analysis

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Abstract

An arteriovenous malformation (AVM) is an abnormal nidus of blood vessels that is characterized by a direct connection between arteries and veins without intervening in the capillary network. The exact underlying cause of sporadic AVMs is unknown, but many studies have reported genetic associations between genes that contribute to angiogenesis, vasculogenesis, and inflammation. Eleven studies retrieved from Medline Complete, PubMed, and Google Scholar up to February 2022 were included. Heterogeneity was assessed using I2 and Q-tests. Publication bias was also assessed for the shortlisted CDKN2B-AS1 rs1333040 (T > C), ACVRL1 rs2071219 (A > G), and rs11169953 (C > T) polymorphisms. The rs1333040 polymorphism showed a lower association with sporadic brain AVM for T versus C in an allelic model (OR = 0.59, 95% confidence interval [CI] = 0.41–0.84). In the recessive model, rs2071219 for AA + AG vs. GG was OR = 0.62, 95% CI = 0.43–0.9. In the recessive model, rs11169953 CC + CT vs. TT was OR = 0.56, 95% CI = 0.33–0.95. In summary, the results of this study support the association between CDKN2B-AS1 and ACVRL1 polymorphisms and sporadic brain arteriovenous malformations. This study summarized the existing information and showed the need for more replication studies on the genetic basis of sporadic AVM. In the future, more genome-wide studies should be conducted to validate and fill existing gaps in knowledge about the mechanisms of sporadic AVM development.

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Data Availability

All data generated or analyzed during this study are included in this article and its supplemental materials. All data used and/or analyzed during this study are available from the corresponding author upon reasonable request.

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Funding

This research was funded by the Ministry of Education and Science of the Republic of Kazakhstan (grant number AP08052031).

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Authors and Affiliations

  1. National Center for Biotechnology, 13/5, Kurgalzhynskoye road, Astana, 010000, Kazakhstan

    Kymbat Mukhtarova, Elena Zholdybayeva, Talgat Utupov & Yerlan Ramankulov

  2. School of Science and Technology, Nazarbayev University, 53 Kabanbay Batyr Ave, 010000, Astana, Kazakhstan

    Yerlan Ramankulov

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  1. Kymbat Mukhtarova
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  2. Elena Zholdybayeva
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  3. Talgat Utupov
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  4. Yerlan Ramankulov
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RY and ZE conceived and designed the study. MK and UT collected data. MK performed the data analysis. MK and ZE drafted the manuscript. All the authors approved the final version of the manuscript.

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Correspondence to Kymbat Mukhtarova.

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Mukhtarova, K., Zholdybayeva, E., Utupov, T. et al. Associations of Reported Genetic Risk Loci with Sporadic Brain Arteriovenous Malformations: Meta-analysis. J Mol Neurosci 72, 2207–2217 (2022). https://doi.org/10.1007/s12031-022-02073-z

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