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SNP rs2043211 (p.C10X) in CARD8 Is Associated with Large-Artery Atherosclerosis Stroke in a Chinese Population

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Abstract

SNP rs2043211 in CARD8 was found to have significant association with ischemic stroke. This study aimed to explore the possible association between rs2043211 and large-artery atherosclerosis stroke in Chinese and explain the possible mechanism. In total, 716 large-artery atherosclerosis stroke patients and 1088 controls were included in the study. Co-dominant, dominant, and recessive genetic models were constructed to evaluate the relationship between rs2043211 and large-artery atherosclerosis stroke risk by odds ratios with 95% confidence intervals. Stratified and interaction analyses were also done. We selected another 111 large-artery atherosclerosis stroke patients and measured the CARD8 levels in their plasma samples by enzyme-linked immunosorbent assay. Participants who carry T/T genotype have a higher risk of large-artery atherosclerosis stroke compared with those carry A/T or A/A genotypes (odds ratio = 1.35, 95% confidence intervals 1.03–1.77, P = 0.029). The higher risk for the T/T genotype is still notable in female, people with hypertension, and people without diabetes. In the interaction analysis, compared to the non-hypertensive participants with the wild homozygote type A/A, the hypertensive participants with the A/T+T/T homozygote had 3.27-fold increased risk (odds ratio = 3.27, 95% confidence intervals 2.33–4.60). The A/A group had lower CARD8 levels in plasma than the A/T and T/T group (P < 0.001). Further bioinformatics prediction indicated that the rs2043211 could significantly influence the mRNA secondary structure and protein expression of CARD8 (eQTL P = 9.8 × 10−198). The rs2043211 is probably a novel biomarker for large-artery atherosclerosis stroke in Chinese.

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Abbreviations

CARD8:

Caspase recruitment domain family, member 8

CI:

Confidence intervals

CT:

Computerized topography

ELISA:

Enzyme-linked immunosorbent assay

eQTL:

Expression quantitative trait loci

GWAS:

Genome-wide association studies

HWE:

Hardy-Weinberg equilibrium

IS:

Ischemic stroke

LAA:

Large-artery atherosclerosis

MRI:

Magnetic resonance imaging

NF-κB:

Nuclear factor-kappa B

NLRP3:

NLR family pyrin domain containing 3

NJSR:

Nanjing Stroke Registry Program

OR:

Odds ratio

SD:

Standard deviations

SNP:

Single nucleotide polymorphism

SVO:

Small vessel occlusive

TOAST:

Trial of Org 10172 in Acute Stroke Treatment

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Acknowledgments

We thank the study participants and the clinical staff for their contribution to this work. We would like to express our gratitude to the director of neurology department Wuzhuang Tang, Jie Li, Zhanyun Ren, Feng Chen, Huihua Zong, Chao Wang, and Wenchao Chen of The Affiliated Yixing Hospital of Jiangsu University for sample collection and data analysis.

Funding

This study was partly supported by the National Natural Science Foundation of China (81771285, 81571148, and 81530038) and the China Postdoctoral Science Foundation (2016M592954).

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Author notes

  1. Jinyu Gu and Chong Shen contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

    Jinyu Gu, Zhizhong Zhang & Xinfeng Liu

  2. Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China

    Chong Shen

  3. Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China

    Mengmeng Gu

  4. Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China

    Mengmeng Wang, Zhizhong Zhang & Xinfeng Liu

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  1. Jinyu Gu
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  2. Chong Shen
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Correspondence to Xinfeng Liu.

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This study was approved by the Ethical Review Committee of Jingling Hospital, Nanjing, China and each participant gave an informed consent before this study.

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Gu, J., Shen, C., Gu, M. et al. SNP rs2043211 (p.C10X) in CARD8 Is Associated with Large-Artery Atherosclerosis Stroke in a Chinese Population. J Mol Neurosci 71, 276–283 (2021). https://doi.org/10.1007/s12031-020-01647-z

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