CYP1A2 phenotype and genotype in a population from the Carboniferous Region of Coahuila, Mexico.
CYP1A2 regulation by polycyclic aromatic hydrocarbons (PAHs) exposure and polymorphism was investigated in 46 male volunteers from the Carboniferous Region in northern Coahuila, Mexico. PAH exposure was estimated by the urinary excretion of 1-hydroxypyrene (1-OHP), whereas the regulatory effects were assessed by the caffeine metabolic ratio (CMR). Genotype was evaluated by determining 5'-flanking region (-2964) and intron I (734) polymorphisms. A statistically significant difference in the urinary 1-OHP geometric means of Barroterán, Cloete and Juárez (2.30, 0.45 and 0.04, respectively) was observed. As for the genotype, the intron I distribution was 0% C/C, 46% C/A and 54% A/A, whereas that of the 5'-flanking region was 26% G/G, 42% G/A and 32% A/A. Both distributions were in agreement with the Hardy-Weinberg equilibrium model. A greater enzyme activity was observed in the A/A compared to C/A individuals according to the CMR (P<0.001), whereas the 5'-flanking region polymorphism showed no effect on CYP1A2 enzymatic activity. These results suggest that intron I polymorphism and PAH exposure are relevant factors that modulate CYP1A2 enzymatic activity.
Castorena-Torres
Fabiola
F
Sección Externa de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Mexico City C.P. 07360, México.
Mendoza-Cantú
Ania
A
de León
Mario Bermúdez
MB
Cisneros
Bulmaro
B
Zapata-Pérez
Omar
O
López-Carrillo
Lizbeth
L
Salinas
Juan E
JE
Albores
Arnulfo
A
D000328:Adult; D002110:Caffeine / Q000378:metabolism / Q000652:urine; D003430:Cross-Sectional Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004781:Environmental Exposure; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008800:Mexico; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000506:poisoning; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011721:Pyrenes / Q000032:analysis; D012989:Soil Pollutants / Q000378:metabolism / Q000506:poisoning
D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D012989:Soil Pollutants; D002110:Caffeine; D004247:DNA; D019388:Cytochrome P-450 CYP1A2; C033146:1-hydroxypyrene