The influence of smoking and homocysteine on subclinical atherosclerosis is modified by the connexin37 C1019T polymorphism - The Cardiovascular Risk in Young Finns Study.
BACKGROUND
A polymorphism C1019T on the connexin37 (Cx37) gene has been found to associate with coronary artery disease. There are conflicting results on which allele confers risk, and the possibility of interactions between the polymorphism and risk factors has been raised. In this study, we examined interactions between the Cx37 polymorphism and common risk factors and their associations to early vascular parameters of atherosclerosis: carotid artery intima-media thickness (IMT), and carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD).


METHODS
A population of 1440 healthy young adults from the Cardiovascular Risk in Young Finns Study was studied. The subjects were genotyped and their cardiovascular risk factor and ultrasound data gathered in 2001 were used for the statistical analyses.


RESULTS
In the whole population, homocysteine in subjects with the TT genotype was found to be associated with higher FMD values (p for interaction 0.038) and remained so in three different adjusted models (p for interaction 0.022-0.038). In women with the CC genotype, smoking was found to be associated with higher FMD values and the smoking-by-genotype interaction remained significant in three adjusted models (p for interaction 0.001-0.041). In women with TT genotype, the effect of smoking was opposite, i.e., FMD values for smokers were lower compared to non-smokers. In men, physical activity interacted with Cx37 on CAC in the CT and TT genotypes (p for interaction 0.011). No significant interactions were found to predict IMT.


CONCLUSIONS
The effect of smoking and homocysteine levels on arterial endothelial functions and elasticity were modified by the allelic variation of the Cx37 gene. These data suggest that variation in the connexin gene may modify effects risk factors have on vascular function.
Collings
Auni
A
Centre for Laboratory Medicine, Tampere University Hospital, and Tampere University Medical School, Tampere, Finland. Auni.Collings@pshp.fi
Raitakari
Olli T
OT
Juonala
Markus
M
Mansikkaniemi
Kristiina
K
Kähönen
Mika
M
Hutri-Kähönen
Nina
N
Marniemi
Jukka
J
Viikari
Jorma S A
JS
Lehtimäki
Terho J
TJ
D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001916:Brachial Artery / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D017630:Connexins / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D005838:Genotype; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D000097006:Gap Junction alpha-4 Protein
D015415:Biomarkers; D017630:Connexins; D006710:Homocysteine; D000097006:Gap Junction alpha-4 Protein