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Chromosome 9p21.3 Variants Are Associated with Cerebral Infarction in Chinese Population

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Abstract

Common variants of chromosome 9p21.3 associated with coronary disease have been established, but the association of 9p21.3 and cerebral infarction (CI) is not consistent. The aim of this study is to confirm the association of cerebral infarction and 9p21.3 in a Chinese Han population. This is a hospital-based case-control study, which involves 769 patients and 682 healthy controls. Eight single-nucleotide polymorphisms (SNPs) associated with cerebral infarction in previous literatures were genotyped and analyzed. The association analyses were performed at both SNP and haplotype levels. Three (rs2383207, rs1537378, and rs3731245) of eight SNPs were associated with cerebral infarction. In an allelic association analysis, rs2383207, rs3731245, and rs1537378 were significantly associated with CI; the odd ratios were 1.18 (95 % confidence interval (CI) = 1.01–1.37, P = 0.04), 1.29 (95 % CI = 1.06–1.56, P = 0.01), and 1.30 (95 % CI = 1.05–1.60, P = 0.02), respectively. rs1537378 remains significantly associated with CI independent of traditional cerebrovascular risk factors in a recessive model (odds ratio (OR) = 1.35, 95 % CI = 1.06–1.71, P = 0.013, Q = 0.03) and in an additive model (OR = 1.38, 95 % CI = 1.11–1.71, P = 0.004, Q = 0.02); conversely, rs2383207 (OR = 1.28, 95 % CI = 1.03–1.59, P = 0.02, Q = 0.03) and rs3731245 (OR = 1.31, 95 % CI = 1.05–1.65, P = 0.02, Q = 0.03) were significantly different in a recessive model. Haplotype analysis showed that the protective effect for haplotype AATAA remained significant (OR = 0.87, 95 % CI = 0.73–1.00, P = 2.99 × 103, Q = 2.15 × 103). These findings showed that chromosome 9p21.3 is an important susceptibility locus for cerebral infarction in Chinese population.

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Abbreviations

SNP:

Single-nucleotide polymorphism

DM:

Diabetes mellitus

CI:

Cerebral infarction

BMI:

Body mass index

CDKN:

Cyclin-dependent kinase inhibitor

AF:

Atrial fibrillation

HWE:

Hardy-Weinberg equilibrium

OR:

Odds ratio

CI:

Confidence interval

GWAS:

Genome-wide association study

ANRIL:

A large antisense noncoding RNA in the INK4 locus

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Acknowledgments

This work was supported by the grant from Nature Science Foundation of China toXL (NSFC 30870847). We thank K. Wood for editing, and Y. Liu, G. Feng, and Y. Li for technical assistance.

Authors’ contribution

The overall design of the study was agreed upon by all authors after extensive discussions. Tian and Fang selected the subjects and conducted the clinical evaluations. Tian and Yue analyzed the data, performed the statistical analysis, and performed data interpretation. Yue conceived of the study, interpreted the data, and wrote the manuscript. Shi, Xu, and Liu conceived the study, interpreted the data, and reviewed the manuscript. All authors read and approved the final manuscript.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China

    Xuanye Yue & Fu-Dong Shi

  2. Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China

    Xuanye Yue, Xinying Fan, Gelin Xu & Xinfeng Liu

  3. Department of Neurology, The Fuyang Hospital, Fuyang, Anhui Province, China

    Lili Tian

Authors
  1. Xuanye Yue
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  2. Lili Tian
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  3. Xinying Fan
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  4. Gelin Xu
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  5. Fu-Dong Shi
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  6. Xinfeng Liu
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Corresponding author

Correspondence to Xinfeng Liu.

Additional information

Xuanye Yue and Lili Tian contributed equally to this work.

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Yue, X., Tian, L., Fan, X. et al. Chromosome 9p21.3 Variants Are Associated with Cerebral Infarction in Chinese Population. J Mol Neurosci 56, 546–552 (2015). https://doi.org/10.1007/s12031-015-0494-9

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  • DOI: https://doi.org/10.1007/s12031-015-0494-9

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