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

Aim: 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 (3.03-4.63) in TT homozygotes, intermediate (1.75-5.24) in heterozygotes, and low (1.75-2.63) in CC homozygotes in systemic arteries except for cerebral and coronary arteries. Conclusion: 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.