Associations between the <i>CDKN2A/B</i>, <i>ADTRP</i> and <i>PDGFD</i> Polymorphisms and the Development of Coronary Atherosclerosis in Japanese Patients
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- Dechamethakun Sariya
- Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University
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- Ikeda Shinobu
- Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University
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- Arai Tomio
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
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- Sato Noriko
- Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University
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- Sawabe Motoji
- Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University
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- Muramatsu Masaaki
- Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University
Bibliographic Information
- Other Title
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- Associations between the CDKN2A/B, ADTRP and PDGFD Polymorphisms and the Development of Coronary Atherosclerosis in Japanese Patients
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Abstract
Aim: Genome-wide association studies have identified a series of susceptibility loci for coronary artery disease(CAD). The present study attempted to replicate the results for eight of these loci, CDKN2A/B(rs1333049), ADTRP(rs6903956), PDGFD(rs974819), TCF21(rs12190287), COL4A1-A2(rs4773144), HHIPL1(rs2895811), ADAMTS7(rs4380028) and UBE2Z(rs46522), in patients with pathologically defined atherosclerosis of the coronary arteries.<br> Methods: Autopsy cases of elderly Japanese subjects were enrolled in the JG-SNP study(n=1,536). Polymorphisms were genotyped, and their associations with the coronary stenosis index(CSI) and incidence of pathological myocardial infraction(MI) were investigated. The potential combinatorial effects of the susceptibility loci were also assessed. <br>Results: Among the eight loci tested, three exhibited signs of positive associations. CDKN2A/B showed the most robust associations with CSI and MI(p=0.007 and OR=1.843, 95% CI 1.293-2.629, p=0.001, for CC＋CG vs. GG). In addition, ADTRP demonstrated associations with CSI and MI, although the risk allele was opposite from that observed in the original report(p=0.008 and OR=1.652, 95% CI 1.027-2.656, p=0.038 for GG vs. AA＋AG). Meanwhile, PDGFD displayed a suggestive association with CSI in women, but not men(p=0.023). CDKN2A/B and ADTRP were also found to be significantly associated with the severity of the CSI in a case-control setting. The cumulative risk allele counting of CDKN2A/B, ADTRP and PDGFD indicated an increased number of risk alleles to be associated with a higher CSI(p=4.61E-05).<br> Conclusions: The present study confirmed the association between CDKN2A/B and CAD and identified a different associated risk allele of ADTRP. PDGFD was found to exhibit a gender-specific association with CAD. The combination of multiple risk alleles may be associated with a higher risk of CAD.
Journal
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- Journal of Atherosclerosis and Thrombosis
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Journal of Atherosclerosis and Thrombosis 21 (7), 680-690, 2014
Japan Atherosclerosis Society
