title: Smoking confers a MTHFR 677C>T genotype-dependent risk for systemic atherosclerosis: results from a large number of elderly autopsy cases that died in a community-based general geriatric hospital.
abstract: OBJECTIVE
  We attempted to explore interactions between smoking and the genetic polymorphism of 24 atherosclerosis-related candidate genes in systemic atherosclerosis.
  
  
  METHODS
  The study comprised 1,503 consecutive autopsy cases. The male-to-female ratio was 1.16 and the average age at death was 80.3 years. Seventy percent of men and 22% of women were current or past smokers. The degree of atherosclerosis in 10 arteries was semi-quantitatively assessed. Melting curve analysis analyzed 34 single nucleotide polymorphisms (SNPs) of 24 genes.
  
  
  RESULTS
  Twenty-four SNPs did not interact with smoking on atherosclerosis, while 7 SNPs interacted in one artery and 2 SNPs in two arteries. The genotypes of MTHFR 677C>T and smoking significantly interacted in four arteries, including the common carotid artery, common and external iliac arteries, and femoral artery. The odds ratios of smoking on atherosclerosis were high (3.034.63) in TT homozygotes, intermediate (1.755.24) in heterozygotes, and low (1.752.63) in CC homozygotes in systemic arteries except for cerebral and coronary arteries.
  
  
  CONCLUSIONS
  MTHFR 677 TT homozygotes are more likely to develop atherosclerosis than heterozygotes or CC homozygotes, if they smoke. Thus, smoking cessation is more important in the prevention of atherosclerosis in MTHFR 677 TT homozygotes.
authors.affiliation: Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan. sawabe@tmig.or.jp
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Araki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hosoi
authors.forename: Aya
authors.initials: A
authors.lastname: Kuchiba
authors.forename: Noriko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Naito
authors.forename: Kanae
authors.initials: K
authors.lastname: Oda
authors.forename: Shinobu
authors.initials: S
authors.lastname: Ikeda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Muramatsu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics; D001344:Autopsy; D005260:Female; D005838:Genotype; D006764:Hospitals, Community; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology / Q000235:genetics
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)