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Fine-Mapping of ABO Gene Identifies Two Novel SNPs Associated with Large Artery Atherosclerotic Stroke in a Chinese Han Population

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Abstract

Recently, a single nucleotide polymorphism (SNP) rs505922 in ABO gene was related to large artery atherosclerotic (LAA) stroke in Caucasian populations by genome-wide association study (GWAS). This study aimed to determine whether ABO gene polymorphisms are associated with LAA stroke in Chinese Han population. A case–control study was designed, and 644 patients with LAA stroke and 642 healthy controls were enrolled. Ten tagging SNPs (tSNPs) located in ABO gene were genotyped. Associations between genotypes and LAA stroke were analyzed with logistic regression model after adjustment of potential confounders. Although rs505922 was not associated with LAA stroke (TT genotype, adjusted OR = 1.32; 95 % CI, 0.94 to 1.87), two novel SNPs, rs8176668 (AT genotype, adjusted OR = 0.71; 95 % CI, 0.55 to 0.92) and rs2073824 (AA genotype, adjusted OR = 0.72; 95 % CI, 0.57 to 0.92), were associated with LAA stroke. Haplotype analysis indicated that haplotype TC (adjusted OR = 0.72; 95 % CI, 0.54 to 0.95; P = 0.018) in block 1 and haplotype ACA in block 2 (OR = 0.73; 95 % CI, 0.58 to 0.91; P = 0.005) were associated with LAA stroke. Multifactor dimensionality reduction (MDR) analysis in the single-locus model indicated that rs2073824 was the most important attributor for predicting risk of LAA stroke. No significant SNP–SNP interactions among the tested SNPs were detected. The results indicated that the genetic variants in ABO gene may influence the risk of LAA stroke in Chinese Han population.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81501027, 81571148, 81501193, and 81220108008) and Hangzhou Science and Technology Bureau Program (20150733Q11). Authors are grateful to all participants for their cooperation in this study. We also thank Miss Ying Lin and Miss Zhaojun Wang in Jinling Hospital, Medical School of Nanjing University, for their technical supports.

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    Authors and Affiliations

    1. Department of Neurology, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China

      Hao Zhang, Zhizhong Zhang, Jun Zhang, Lili Xu, Biyang Cai, Shuyu Zhou, Lingli Sun, Wen Sun, Xinfeng Liu & Gelin Xu

    2. Department of Neurology, The First People’s Hospital of Hangzhou, Nanjing Medical University, Hangzhou, 310006, Zhejiang, China

      Hao Zhang

    3. Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, 210002, Jiangsu, China

      Zusen Ye, Yonggang Hao, Keting Liu, Huan Cai & Guihua Ni

    4. Department of Gerontology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, Jiangsu, China

      Yumeng Zhang

    5. Department of Neurology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, 223300, Jiangsu, China

      Guihua Ni

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    1. Hao Zhang
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    Correspondence to Gelin Xu.

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    Hao Zhang and Zhizhong Zhang contributed equally to this work.

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    Zhang, H., Zhang, Z., Zhang, J. et al. Fine-Mapping of ABO Gene Identifies Two Novel SNPs Associated with Large Artery Atherosclerotic Stroke in a Chinese Han Population. Mol Neurobiol 54, 2107–2113 (2017). https://doi.org/10.1007/s12035-016-9794-5

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