Cyp1B1 mRNA expression in correlation to cotinine levels with respect to the Cyp1B1 L432V gene polymorphism.
Cytochrome P450 1B1 (CYP1B1) is involved in the activation of a broad spectrum of procarcinogens. An association of the Cyp1B1 Leu432Val polymorphism with cancer as well as an impact on the enzyme activity has been described. To study gene-environmental interactions we investigated the quantitative Cyp1B1 mRNA expression in smokers (N = 102) and non-smokers (N = 192) with regards to the Cyp1B1 L432V gene polymorphism. Tobacco smoke exposure was assessed by serum cotinine levels. Genotypes were analysed by melting curve analysis and quantification of Cyp1B1 mRNA by real-time PCR. In comparing Cyp1B1 expression, significant differences between the two homozygote genotypes *1/*1 and *3/*3 (0.105 ± 0.019; n = 26 vs. 0.051 ± 0.017; n = 14; P = 0.039) and between the heterozygote genotype *1/*3 and *3/*3 (0.121 ± 0.029; n = 55 vs. 0.051 ± 0.017; n = 14; P = 0.039) of smokers were revealed. According to the serum cotinine levels, three subgroups (low; medium; high) were build. The group "high" (0.248 ± 0.089; n = 32) showed proportionally high Cyp1B1 mRNA expression compared to "medium" (0.101 ± 0.024; n = 33), "low" (0.086 ± 0.015; n = 32) and non-smokers (0.084 ± 0.007; n = 176). This result was reflected in the homozygote *1/*1 and the heterozygote *1/*3 genotypes. In contrast the homozygote *3/*3 genotype was missing the high Cyp1B1 mRNA expression in the cotinine subgroup "high". Our results suggest that genotypes carrying the C-allele (*1/*1 and *1/*3) at Cyp1B1 Leu432Val polymorphism show a higher response to environmental factors, such as tobacco smoke than homozygote *3/*3 genotypes.
Helmig
Simone
S
Institut und Poliklinik für Arbeits- und Sozialmedizin, der Justus-Liebig Universität, Aulweg 129, 35392 Giessen, Germany. Simone.Helmig@arbmed.med.uni-giessen.de
Seelinger
Jens Udo
JU
Philipp-Gehlhaar
Monika
M
Döhrel
Juliane
J
Schneider
Joachim
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D003367:Cotinine / Q000097:blood*; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D015870:Gene Expression; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012907:Smoking / Q000097:blood / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D012333:RNA, Messenger; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D003367:Cotinine