Shanshan Chen1, Xiaojing Wang1, Junhan Wang2, Yuanyuan Zhao1, Dan Wang1, Chengcheng Tan1, Jingjing Fa1, Rongfeng Zhang3, Fan Wang1, Chaoping Xu1, Yufeng Huang1, Sisi Li1, Dan Yin1, Xin Xiong1, Xiuchun Li1, Qiuyun Chen4, Xin Tu1, Yanzong Yang3, Yonglong Xia3, Chengqi Xu1, Qing K Wang1,4. 1. Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China. 2. Department of Clinical Laboratory, University Hospital, Huazhong University of Science and Technology, Wuhan, China. 3. Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, China. 4. Center for Cardiovascular Genetics, Department of Molecular Cardiology, Cleveland Clinic, and Department of Molecular Medicine, CCLCM, Case Western Reserve University, Cleveland, OH 44195, USA.
Abstract
BACKGROUND: The CAV1 gene encodes caveolin-1 expressed in cell types relevant to atherosclerosis. Cav-1-null mice showed a protective effect on atherosclerosis under the ApoE(-/-) background. However, it is unknown whether CAV1 is linked to CAD and MI in humans. In this study we analyzed a tagSNP for CAV1 in intron 2, rs3807989, for potential association with CAD. METHODS AND RESULTS: We performed case-control association studies in three independent Chinese Han populations from GeneID, including 1249 CAD cases and 841 controls in Population I, 1260 cases and 833 controls in Population II and 790 cases and 1212 controls in Population III (a total of 3299 cases and 2886 controls). We identified significant association between rs3807989 and CAD in three independent populations and in the combined population (Padj = 2.18 × 10(-5), OR = 1.19 for minor allele A). We also detected significant association between rs3807989 and MI (Padj = 5.43 × 10(-5), OR = 1.23 for allele A). Allele A of SNP rs3807989 was also associated with a decreased level of LDL cholesterol. Although rs3807989 is a tagSNP for both CAV1 and nearby CAV2, allele A of SNP rs3807989 was associated with an increased expression level of CAV1 (both mRNA and protein), but not CAV2. CONCLUSIONS: The data in this study demonstrated that rs3807989 at the CAV1/CAV2 locus was associated with significant risk of CAD and MI by increasing expression of CAV1 (but not CAV2). Thus, CAV1 becomes a strong candidate susceptibility gene for CAD/MI in humans.
BACKGROUND: The CAV1 gene encodes caveolin-1 expressed in cell types relevant to atherosclerosis. Cav-1-null mice showed a protective effect on atherosclerosis under the ApoE(-/-) background. However, it is unknown whether CAV1 is linked to CAD and MI in humans. In this study we analyzed a tagSNP for CAV1 in intron 2, rs3807989, for potential association with CAD. METHODS AND RESULTS: We performed case-control association studies in three independent Chinese Han populations from GeneID, including 1249 CAD cases and 841 controls in Population I, 1260 cases and 833 controls in Population II and 790 cases and 1212 controls in Population III (a total of 3299 cases and 2886 controls). We identified significant association between rs3807989 and CAD in three independent populations and in the combined population (Padj = 2.18 × 10(-5), OR = 1.19 for minor allele A). We also detected significant association between rs3807989 and MI (Padj = 5.43 × 10(-5), OR = 1.23 for allele A). Allele A of SNP rs3807989 was also associated with a decreased level of LDL cholesterol. Although rs3807989 is a tagSNP for both CAV1 and nearby CAV2, allele A of SNP rs3807989 was associated with an increased expression level of CAV1 (both mRNA and protein), but not CAV2. CONCLUSIONS: The data in this study demonstrated that rs3807989 at the CAV1/CAV2 locus was associated with significant risk of CAD and MI by increasing expression of CAV1 (but not CAV2). Thus, CAV1 becomes a strong candidate susceptibility gene for CAD/MI in humans.
Keywords:
Atherosclerosis; CAV1 and CAV2; Coronary artery disease (CAD) and myocardial infarction (MI); Genome-wide association study (GWAS); Single nucleotide polymorphism (SNP); rs3807989
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