Interaction between CYP1A1 T3801C and AHR G1661A polymorphisms according to smoking status on blood pressure in the Stanislas cohort.
BACKGROUND
CYP1A1, one of the key enzymes in detoxifying toxic components produced during cigarette smoking, is regulated by aromatic hydrocarbon receptor (AHR). A CYP1A1 T3801C polymorphism, associated with a higher CYP1A1 inducibility and enhanced catalytic activity, has been linked to stroke, triple vessel disease and may, therefore, be associated with blood pressure (BP). The relation of the widely studied G1661A polymorphism of the human AHR gene with BP is unknown.


OBJECTIVE
To investigate the genetic influence of CYP1A1 T3801C and AHR G1661A polymorphisms on BP in relation to tobacco consumption.


METHODS
Study participants were selected from a French longitudinal cohort of volunteers for a free health check-up. These individuals (302 men and 311 women) were not taking medication that can affect blood pressure. Information about active smoking status was obtained by a self-administered questionnaire.


RESULTS
After multiple regression analysis, systolic blood pressure (SBP) and diastolic blood pressure (DBP) did not differ significantly according to their tobacco status excepted for DBP in men. In addition, neither CYP1A1 T3801C nor AHR G1661A polymorphism was linked to blood pressure. However, systolic and diastolic blood pressures differed significantly according to CYP1A1 T3801C genotype between ex-smokers and smokers. Finally, the interaction between CYP1A1 T3801C and AHR G1661A polymorphisms explained a significant difference of SBP and DBP between carriers of both CYP1A1-C3801 and AHR-A1661 alleles.


CONCLUSIONS
This study is the first to show an interaction between the CYP1A1 T3801C and AHR G1661A polymorphisms. This interaction could explain the difference in blood pressure level between smokers and non-smokers/ex-smokers but needs to be confirmed in a large sample.
Gambier
Nicolas
N
INSERM U525, Faculté de Pharmacie, Université Henri Poincaré Nancy 1, Nancy, France.
Marteau
Jean-Brice
JB
Batt
Anne-Marie
AM
Marie
Bérangère
B
Thompson
Annick
A
Siest
Gérard
G
Foernzler
Dorothee
D
Visvikis-Siest
Sophie
S
D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D015331:Cohort Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human