title: Association of the RYR3 gene polymorphisms with atherosclerosis in elderly Japanese population.
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).
  
  
  CONCLUSIONS
  rs877087 and rs2229116 of RYR3 gene are associated with atherosclerosis severity in Japanese. The functional difference caused by rs2229116 needs to be investigated.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhao
authors.forename: Shinobu
authors.initials: S
authors.lastname: Ikeda
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Makiko
authors.initials: M
authors.lastname: Naka-Mieno
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. muramatsu.epi@mri.tmd.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001344:Autopsy; D002340:Carotid Artery Diseases / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D017536:Carotid Artery, Common / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel