Variants in COMT and spontaneous smoking cessation: retrospective cohort analysis of 925 cessation events.
Genome-wide studies have identified single nucleotide polymorphisms associated with smoking behaviour and nicotine dependence. Less is known about genetic determinants of smoking cessation, but rs4680 in COMT has recently been shown to explain a substantial proportion of the variation in cessation in the general population. We attempted to replicate the reported, clinically relevant effect in a population-based retrospective cohort analysis of 1443 ever-heavy smokers, of whom 925 had reached abstinence. In Cox regression models, neither rs4680 nor two polymorphisms nearby were associated with smoking cessation. The adjusted relative cessation rate (95% confidence interval) in rs4680 methionine carriers in reference to valine homozygotes was 0.97 (0.83-1.12). The absence of a significant effect of rs4680 in this statistically well-powered study - the 95% confidence interval even excluding the previously reported effect - highlights the need for rigorous replication efforts and suggests that rs4680 genotype should not yet be considered informative for smoking patient care.
Breitling
Lutz Philipp
LP
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. L.Breitling@dkfz.de
Dahmen
Norbert
N
Illig
Thomas
T
Rujescu
Dan
D
Nitz
Barbara
B
Raum
Elke
E
Winterer
Georg
G
Rothenbacher
Dietrich
D
Brenner
Hermann
H
D000368:Aged; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000502:physiology; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D012907:Smoking / Q000235:genetics*; D016540:Smoking Cessation / Q000379:methods*
D002394:Catechol O-Methyltransferase