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Open Access Highly Accessed Research article

Association of the RYR3 gene polymorphisms with atherosclerosis in elderly Japanese population

Chenxi Zhao1, Shinobu Ikeda1, Tomio Arai2, Makiko Naka-Mieno3, Noriko Sato1, Masaaki Muramatsu1* and Motoji Sawabe4

Author Affiliations

1 Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan

2 Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

3 Department of Medical Informatics, Center of Information, Jichii Medical University, Tochigi, Japan

4 Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan

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BMC Cardiovascular Disorders 2014, 14:6  doi:10.1186/1471-2261-14-6

Published: 14 January 2014

Abstract

Background

The Ryanodine receptor 3 gene (RYR3) encodes an intracellular calcium channel that mediates the efflux of Ca2+ from intracellular stores. Two single-nucleotide polymorphisms (SNPs) in the RYR3 gene have been shown to associate with stroke (rs877087) and carotid intima-media thickness (rs2229116) in two independent genome-wide association studies (GWAS) in Caucasian. We investigated the effect of these two SNPs as well as the 31.1 kilobases spanning region on atherosclerosis in Japanese population.

Methods

Atherosclerotic severity was assessed by carotid artery (n = 1374) and pathological atherosclerosis index (PAI) (n = 1262), which is a macroscopic examination of the luminal surfaces of 8 systemic arteries in consecutive autopsy samples. 4 tag SNPs in the 31.1 Kb region, rs877087, rs2132207, rs658750 and rs2229116, were genotyped and haplotypes were inferred to study the association with atherosclerotic indices.

Results

rs877087 and rs2229116 were associated with PAI (OR = 2.07 [1.04-4.12] (95% CI), p = 0.038; and OR = 1.38 [1.02-1.86], p = 0.035, respectively). rs2229116 was also associated with common carotid atherosclerosis (OR = 1.45 [1.13-1.86], p = 0.003). The risk allele of rs2229116 was opposite from the original report. The haplotype block of this 31.1 Kb region was different between Caucasian and Japanese. Haplotype analysis revealed that only TAGG haplotype was associated with PAI (OR = 0.67 [0.48-0.94], p = 0.020) and atherosclerosis of common carotid artery (OR = 0.75 [0.58-0.98], p = 0.034).

Conclusion

rs877087 and rs2229116 of RYR3 gene are associated with atherosclerosis severity in Japanese. The functional difference caused by rs2229116 needs to be investigated.

Keywords:
Atherosclerosis; Polymorphism; Ryanodine receptor 3; Japanese