Association of SNP rs17465637 on Chromosome 1q41 and rs599839 on 1p13.3 with Myocardial Infarction in an American Caucasian Population

Authors

  • Annabel Z. Wang,

    1. Center for Cardiovascular Genetics, Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, USA
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    • A.Z.W. and L.L. made equal contributions to this work.

  • Lin Li,

    1. Center for Cardiovascular Genetics, Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, USA
    2. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, OH, USA
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    • A.Z.W. and L.L. made equal contributions to this work.

  • Bin Zhang,

    1. Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
    2. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, OH, USA
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  • Gong-Qing Shen,

    Corresponding author
    1. Center for Cardiovascular Genetics, Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, USA
    2. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, OH, USA
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  • Qing Kenneth Wang

    Corresponding author
    1. Center for Cardiovascular Genetics, Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH, USA
    2. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, OH, USA
    3. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, P. R. China
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Corresponding author: Dr. Qing K. Wang or Dr. Gong-Qing Shen, Center for Cardiovascular Genetics/NE40, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195. Tel: 216 445 0570; Fax: 216 636 1231; E-mail wangq2@ccf.org or sheng@ccf.org

Summary

Recent genome-wide single nucleotide polymorphism (SNP) association studies (GWAS) have identified a number of SNPs that were significantly associated with coronary artery disease and myocardial infarction (MI). However, many independent replication studies in other populations are needed to unequivocally confirm the GWAS association. To assess GWAS association, we have established a case-control cohort consisting of 1231 well-characterised MI patients and 560 controls without detectable coronary stenosis, all selected from the Cleveland Genebank population. The Genebank cohort has sufficient power to detect the association between MI and four GWAS SNPs, including rs17465637 within the MIA3 gene, rs2943634 (intergenic), rs6922269 in MTHFD1L, and rs599839 near SORT1. SNPs were genotyped by TaqMan assays and follow-up multivariate logistic regression analysis with incorporation of significant covariates showed significant association with MI for MIA3 SNP rs17465637 (P-adj= 0.0034) and SORT1 SNP rs599839 (P-adj= 0.009). The minor allele G of rs599839 was also associated with a decreased LDL-C level of 5–9 mg/dL per allele, but not with HDL-C or triglyceride levels. No association for MI or lipid levels was found for SNPs rs2943634 and rs6922269 (P-adj > 0.05). Our results establish two SNPs, rs17465637 in MIA3 and rs599839 near SORT1 as significant risk factors for MI in the American Genebank Caucasian population.

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