Interaction between a polymorphism of the apo A-I promoter region and smoking determines plasma levels of HDL and apo A-I.
Epidemiological studies have demonstrated that the risk of coronary artery disease (CAD) is increased in smokers but reduced in individuals with elevated plasma levels of high density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I. In a sample of 315 men and women from Iceland, the mean levels of HDL-C and apo A-I in smokers were, respectively, 12% and 6% lower in men and 7% and 6% lower in women compared with nonsmokers. In the men who were nonsmokers, a guanine (G) to adenine (A) (G/A) substitution 75 bp upstream from the start of transcription of the apo A-I gene was associated with elevated levels of HDL-C and apo A-I, with those carrying the A allele having levels of HDL-C and apo A-I roughly 10% higher than those with only the G allele. This genotype effect was abolished in the men who smoked and absent in the sample of women. Based on the reported protective effect associated with elevated levels of apo A-I and HDL-C, men carrying the A allele would have roughly a 20% lower relative risk of CAD compared with those without the A allele, but only if they remained nonsmokers. This gene polymorphism would therefore be an important factor in determining those men who would most benefit from avoidance or cessation of smoking. Determining the mechanism of such interaction between genotype and environment will be important in understanding the etiology of CAD.
Sigurdsson
G
G
Charing Cross Sunley Research Centre, London, UK.
Gudnason
V
V
Sigurdsson
G
G
Humphries
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SE
D000293:Adolescent; D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000032:analysis / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000097:blood*
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL