Abstract
A large-scale meta-analysis of 14 genome-wide association studies has identified and replicated a series of susceptibility polymorphisms for coronary artery disease (CAD) in European ancestry populations, but evidences for the associations of these loci with CAD in other ethnicities remain lacking. Herein we investigated the associations between ten (rs579459, rs12413409, rs964184, rs4773144, rs2895811, rs3825807, rs216172, rs12936587, rs46522 and rs3798220) of these loci and CAD in Southern Han Chinese (CHS). Genotyping was performed in 1716 CAD patients and 1572 controls using mass spectrography. Both allelic and genotypic associations of rs964184, rs2895811 and rs3798220 with CAD were significant, regardless of adjustment for covariates of gender, age, hypertension, type 2 diabetes, blood lipid profiles and smoking. Significant association of rs12413409 was initially not observed, but after the adjustment for the covariates, both allelic and genotypic associations were identified as significant. Neither allelic nor genotypic association of the other six polymorphisms with CAD was significant regardless of the adjustment. Our results indicated that four loci of the total 10 were associated with CAD in CHS. Therefore, some of the CAD-related loci in European ancestry populations are indeed susceptibility loci for the risk of CAD in Han Chinese.
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References
Marenberg, M. E., Risch, N., Berkman, L. F., Floderus, B. & de Faire, U. Genetic susceptibility to death from coronary heart disease in a study of twins. N. Engl. J. Med. 330, 1041–1046 (1994).
Wang, L., Fan, C., Topol, S. E., Topol, E. J. & Wang, Q. Mutation of MEF2A in an inherited disorder with features of coronary artery disease. Science 302, 1578–1581 (2003).
Roberts, R. Genetics of coronary artery disease: an update. Methodist Debakey Cardiovasc. J. 10, 7–12 (2014).
Roberts, R. Genetics of coronary artery disease. Circ. Res. 114, 1890–1903 (2014).
Willer, C. J., Sanna, S., Jackson, A. U., Scuteri, A., Bonnycastle, L. L., Clarke, R. et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat. Genet. 40, 161–169 (2008).
Myocardial Infarction Genetics Consortium, Kathiresan, S., Voight, B. F., Purcell, S., Musunuru, K., Ardissino, D. et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat. Genet. 41, 334–341 (2009).
Coronary Artery Disease (C4D) Genetics Consortium A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat. Genet. 43, 339–344 (2011).
Lu, X., Wang, L., Chen, S., He, L., Yang, X., Shi, Y. et al. Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease. Nat. Genet. 44, 890–894 (2012).
Dechamethakun, S., Ikeda, S., Arai, T., Sato, N., Sawabe, M. & Muramatsu, M. Associations between the CDKN2A/B, ADTRP and PDGFD Polymorphisms and the development of coronary atherosclerosis in Japanese patients. J. Atheroscler. Thromb. 21, 680–690 (2014).
Schunkert, H., König, I. R., Kathiresan, S., Reilly, M. P., Assimes, T. L., Holm, H. et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat. Genet. 43, 333–338 (2011).
Clarke, R., Peden, J. F., Hopewell, J. C., Kyriakou, T., Goel, A., Heath, S. C. et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N. Engl. J. Med. 361, 2518–2528 (2009).
Weissglas-Volkov, D., Aguilar-Salinas, C. A., Sinsheimer, J. S., Riba, L., Huertas-Vazquez, A., Ordonez-Sanchez, M. L. et al. Investigation of variants identified in caucasian genome-wide association studies for plasma high-density lipoprotein cholesterol and triglycerides levels in Mexican dyslipidemic study samples. Circ. Cardiovasc. Genet. 3, 31–38 (2010).
Kristiansson, K., Perola, M., Tikkanen, E., Kettunen, J., Surakka, I., Havulinna, A. S. et al. Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits. Circ. Cardiovasc. Genet. 5, 242–249 (2012).
Braun, T. R., Been, L. F., Singhal, A., Worsham, J., Ralhan, S., Wander, G. S. et al. A replication study of GWAS-derived lipid genes in Asian Indians: the chromosomal region 11q23.3 harbors loci contributing to triglycerides. PLoS ONE 7, e37056 (2012).
Shen, Y., Xi, B., Zhao, X., Cheng, H., Hou, D., Wu, L. et al. Common genetic variants associated with lipid profiles in a Chinese pediatric population. Hum. Genet. 132, 1275–1285 (2013).
Weissglas-Volkov, D., Aguilar-Salinas, C. A., Nikkola, E., Deere, K. A., Cruz-Bautista, I., Arellano-Campos, O. et al. Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci. J. Med. Genet. 50, 298–308 (2013).
Tokoro, F., Matsuoka, R., Abe, S., Arai, M., Noda, T., Watanabe, S. et al. Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus. Biomed. Rep. 3, 88–92 (2015).
Wu, Y., Yu, S., Wang, S., Shi, J., Xu, Z., Zhang, Q. et al. Zinc finger protein 259 (ZNF259) polymorphisms are associated with the risk of metabolic syndrome in a han chinese population. Clin. Lab. 61, 615–621 (2015).
Xu, L., Zhou, J., Huang, S., Huang, Y., Le, Y., Jiang, D. et al. An association study between genetic polymorphisms related to lipoprotein-associated phospholipase A(2) and coronary heart disease. Exp. Ther. Med. 5, 742–750 (2013).
Luke, M. M., Kane, J. P., Liu, D. M., Rowland, C. M., Shiffman, D., Cassano, J. et al. A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease. Arterioscler. Thromb. Vasc. Biol. 27, 2030–2036 (2007).
Shiffman, D., Louie, J. Z., Rowland, C. M., Malloy, M. J., Kane, J. P. & Devlin, J. J. Single variants can explain the association between coronary heart disease and haplotypes in the apolipoprotein(a) locus. Atherosclerosis 212, 193–196 (2010).
Koch, W., Mueller, J. C., Schrempf, M., Wolferstetter, H., Kirchhofer, J., Schomig, A. et al. Two rare variants explain association with acute myocardial infarction in an extended genomic region including the apolipoprotein (A) gene. Ann. Hum. Genet. 77, 47–55 (2013).
Wang, Y., Wang, L., Liu, X., Zhang, Y., Yu, L., Zhang, F. et al. Genetic variants associated with myocardial infarction and the risk factors in Chinese population. PLoS ONE 9, e86332 (2014).
Matsuoka, R., Abe, S., Tokoro, F., Arai, M., Noda, T., Watanabe, S. et al. Association of six genetic variants with myocardial infarction. Int. J. Mol. Med. 35, 1451–1459 (2015).
Wauters, E., Carruthers, K. F., Buysschaert, I., Dunbar, D. R., Peuteman, G., Belmans, A. et al. Influence of 23 coronary artery disease variants on recurrent myocardial infarction or cardiac death: the GRACE Genetics Study. Eur. Heart J. 34, 993–1001 (2013).
Kiechl, S., Paré, G., Barbalic, M., Qi, L., Dupuis, J., Dehghan, A. et al. Association of variation at the ABO locus with circulating levels of soluble intercellular adhesion molecule-1, soluble P-selectin, and soluble E-selectin: a meta-analysis. Circ. Cardiovasc. Genet 4, 681–686 (2011).
LĂłpez-MejĂas, R., Genre, F., GarcĂa-BermĂşdez, M., Ubilla, B., Castañeda, S., Llorca, J. et al. Lack of association between ABO, PPAP2B, ADAMST7, PIK3CG, and EDNRA and carotid intima-media thickness, carotid plaques, and cardiovascular disease in patients with rheumatoid arthritis. Mediators Inflamm. 2014, 756279 (2014).
Acknowledgements
We thank all the participants for their support and participation. This study was funded by the National Natural Science Foundation of China (81302616 and 81430046), the China Postdoctoral Science Foundation (2013M542226), Guangdong Provincial Key Laboratory of Forensic Genetics (2010A060801001), the China National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (2012BAK02B02).
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Huang, EW., Peng, LY., Zheng, JX. et al. Investigation of associations between ten polymorphisms and the risk of coronary artery disease in Southern Han Chinese. J Hum Genet 61, 389–393 (2016). https://doi.org/10.1038/jhg.2015.158
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DOI: https://doi.org/10.1038/jhg.2015.158