From: Genetics of Tobacco Use
First Author, Year | Population, Sample size | Genea | Statistically Significant (p < 0.05) Results |
---|---|---|---|
Xu 2002 | Canada N = 14 in kinetic substudy N = 478 in allele frequency study | Wild-type CYP2A6*1/*1 vs. *4/*4, *4/*10, *4/*7, *7/*7, *1/*8 | Homozygous wild-type genotypes CYP2A6*1/1 have lower plasma levels of nicotine and higher levels of the CYP2A6-mediated nicotine metabolite cotinine, compared to those with the null *4/4 genotype (6 hours after oral administration of nicotine) |
*7/*7 genotypes or *7 in combination with gene deletion have intermediate levels of nicotine | |||
One individual containing both *7 and *8 (CYP2A6*4/*10) has sharply reduced metabolism of both nicotine and cotinine | |||
Rao 2000 | Canada N = 296 smokers | CYP2A6*1/*1 vs. *1/*4, *1/2, *2/2, or *1/*1 plus duplication | Smokers with reduced activity or null alleles (*2/2, *1/2 or *1/4) use fewer cigarettes/day compared to those with wild-type (*1/*1) genotype both currently (13.5 ± 2.3 vs. 19.5 ± 0.7) and at time of heaviest smoking (19 vs. 29), and have lower cotinine Levels |
Kitagawa 1999 | Japan N = 11 smokers in smoking challenge sub-study N = 252 in genotype study | CYP2A6*1/1 vs. homozygous deletion | Homozygous wild-type genotypes CYP2A6*1/1 have higher cotinine concentrations in urine than homozygously deleted genotypes (average concentration 3.87 ± 1.64 vs. 0.40 ± 0.15 ③ g/ml at 1.5 hours after smoking for 1 hr.) |
On average over the 24-hr period following smoking challenge, cotinine excretion in homozygously deleted genotypes was one-seventh compared to control group (p < 0.001) | |||
Pianezza 1998 | Canada N = 428 | CYP2A6*1/1 vs. null alleles *2 or *3 | Dependent smokers have lower frequency of null alleles, compared to the never-dependent control group (12.3% vs. 19.6%, p < 0.04, OR = 1.74, 95% CI 1.02–2.94) |
Smokers heterozygous for null alleles have fewer number of cigarettes/week (129 vs. 159, t-test p < 0.02), compared to smokers with two active alleles |