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Association of genetic variants of RNF213 with ischemic stroke risk in Koreans

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Abstract

Background

Large artery disease (LAD), cardioembolism (CE), and small vessel disease (SVD) are well-established causes of ischemic stroke. Although a founder variant of RNF213 has been regarded a genetic susceptibility for Moyamoya disease (MMD) and certain types of intracranial atherosclerotic stenosis (ICAS), correlations between RNF213 variants and ischemic stroke with SVD remain largely unknown.

Objectives

This study aimed to characterize the associations of four RNF213 polymorphisms (4448G>A, 4810G>A, 4863G>A, and 4950G>A) with ischemic stroke subtypes in Koreans.

Methods

Genetic data from 529 stroke patients were analyzed and compared to 424 age- and sex-matched controls. Genetic variants of RNF213, as obtained from the Human Gene Mutation Database, were analyzed in the study subjects using the polymerase chain reaction restriction fragment length polymorphism assay. We investigated four single-nucleotide polymorphisms of RNF213 to elucidate their association with ischemic stroke [LAD, (n = 192), SVD (n = 145) and CE (n = 51)].

Results

The RNF213 4950G>A genotype was observed more frequently in cerebral stroke patients and was more strongly associated with SVD than LAD (P = 0.014). RNF213 4448/4950 in combination with G–A was higher in SVD patients. However, the RNF213 4863/4950 allele combination was associated with increased risk of SVD and LAD. These results confirmed that RNF213 4950GA+AA variants were more frequent in ischemic stroke, especially in SVD, and that RNF213 G–G–G–A and G–G–G–A (4448/4810/4863/4950) haplotype sequences play a role in LAD and CE as well as SVD.

Conclusions

Our data reported that the RNF213 4950G>A genotypes and several RNF213 (4448/4810/4863/4950) haplotypes were associated with ischemic stroke in Koreans.

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Acknowledgements

This study was supported by Grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2016R1D1A1B03930141, NRF-2017R1D1A1B03030110 and NRF-2018R1D1A1A09082764).

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Author notes

  1. Young Seok Park and Hyeon Woo Park contributed equally in this work.

Authors and Affiliations

  1. Department of Neurosurgery, College of Medicine, Chungbuk National University Hospital, Chungbuk National University, Cheongju, South Korea

    Young Seok Park

  2. Department of Biomedical Science, College of Life Science, CHA University, Seongnam, 13488, South Korea

    Hyeon Woo Park, Han Sung Park, Chang Soo Ryu, Jeong Yong Lee, Eun Ju Ko & Nam Keun Kim

  3. Department of Cardiology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea

    Jung Hoon Sung

  4. Department of Neurology, CHA Bundang Medical Center, CHA University School of Medicine, 59, Yatap-ro, BundanG–Gu, Seongnam, 13496, South Korea

    Jinkwon Kim & Ok Joon Kim

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  1. Young Seok Park
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  2. Hyeon Woo Park
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  3. Han Sung Park
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  7. Jung Hoon Sung
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  8. Jinkwon Kim
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  9. Ok Joon Kim
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  10. Nam Keun Kim
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Corresponding authors

Correspondence to Ok Joon Kim or Nam Keun Kim.

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Conflict of interest

Young Seok Park, Hyeon Woo Park, Han Sung Park, Chang Soo Ryu, Jeong Yong Lee, Eun Ju Ko, Jung Hoon Sung, Jinkwon Kim, Ok Joon Kim, Nam Keun Kim declare that they have no conflict of interest.

Ethical approval

This study had been approved by the Institutional Review Board of CHA Bundang Medical Center (IRB number: BD2010-123D) and written informed consent was provided by all patients.

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Park, Y.S., Park, H.W., Park, H.S. et al. Association of genetic variants of RNF213 with ischemic stroke risk in Koreans. Genes Genom 43, 389–397 (2021). https://doi.org/10.1007/s13258-020-01022-7

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  • DOI: https://doi.org/10.1007/s13258-020-01022-7

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