The Interaction of Genes and Smoking on Forced Expiratory Volume: A Classic Twin Study.

Chest. 2007 Nov 7
Zhai G, Valdes AM, Cherkas L, Clement G, Strachan D, Spector TD.
Twin Research & Genetic Epidemiology Unit, King's College London School of Medicine, UK.

Genetic influences on lung function measured by the forced expiratory volume in one second (FEV(1)) have been reported from twin and family studies. The aim of this study was to estimate heritability of the ratio of measured (mFEV(1)) to expected (eFEV(1)) FEV(1) in a Caucasian population and to examine the interaction between genetic factors and smoking on this ratio.

Methods and subjects
The sample consisted of unselected monozygotic (MZ) and dizygotic (DZ) twin pairs from the TwinsUK registry. FEV(1) was measured with a spirometer and the ratio of mFEV(1) to eFEV(1) was calculated.

A total of 475 MZ and 1054 DZ twin pairs with a mean age of 47 (range 18 - 84) participated. The ratio of mFEV(1) to eFEV(1) was 0.057 lower in smokers than non-smokers (p<0.0001). The difference in the correlation for the mFEV(1) to eFEV(1) ratio between MZ and DZ twin pairs was 0.32 in non-smokers and 0.19 in current smokers, suggesting a significant genetic influence on lung function that was modified in current smokers. Using structural equation modelling, the heritability estimate for the mFEV(1) to eFEV(1) ratio was found to be 66% (95% CI 59 - 72%) in non-smokers but significantly reduced to 32% (95% CI 12 - 53%) in current smokers. However, there was no clear difference in the heritability of the mFEV(1) to eFEV(1) ratio between non-smokers and ex-smokers.

Genes are the major influence on the variability of the ratio of mFEV(1) to eFEV(1) in non-smokers. However, this strong genetic influence is strongly modified by an interaction with cigarettes.

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