Genetic Polymorphism of CYP2C19 gene in the Stanislas cohort. A link with inflammation.
CYP2C19, a member of the cytochrome P450 family, metabolises arachidonic acid to produce epoxyeicosanoid acids, which are involved in vascular tone and inflammation. Thus, this study describes the possible relationship between a CYP2C19 polymorphism (681G>A) and three inflammatory markers: interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha) and high sensitivity C-reactive protein (hs-CRP) in healthy individuals. In a sub-sample of 178 men and 181 women from the Stanislas study, we quantified plasma IL-6 and TNF-alpha concentrations by using an enzyme-linked immunosorbent assay, and serum hs-CRP concentration by immunonephelometry. The CYP2C19 681G>A polymorphism was genotyped using the kinetic thermocycling allele specific PCR method. In the Stanislas cohort, the frequency of the allele CYP2C19*2 (681A) was 17.8%. Circulating levels of inflammatory factors were increased in individuals homozygous for the defective allele CYP2C19*2 (A) notably IL-6 in the whole sample (P= 0.0008) and hs-CRP only in women (P= 0.008), with a significant interaction with sex (P= 0.005), in comparison to carriers of one copy or more of the wild type allele CYP2C19*1 (G). Only a trend of association (P= 0.089) was found between this polymorphism and TNF-alpha concentration in the whole sample. The association between CYP2C19*2 polymorphism and inflammatory markers' concentrations could suggest that CYP2C19 may be considered as a new candidate gene for cardiovascular risks via inflammation.
Bertrand-Thiébault
C
C
INSERM U525, Faculté de Pharmacie, 30 rue Lionnois, Nancy, France.
Berrahmoune
H
H
Thompson
A
A
Marie
B
B
Droesch
S
S
Siest
G
G
Foernzler
D
D
Visvikis-Siest
S
S
D000328:Adult; D000704:Analysis of Variance; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005602:France; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009391:Nephelometry and Turbidimetry; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D044465:White People / Q000235:genetics
D017931:DNA Primers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19