Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans

Abstract

We found significant differences in CYP1A2 enzyme activity between Swedes and Koreans that could not be explained by environmental factors or the CYP1A2 haplotypes examined, despite differences in allele frequencies. None of the investigated CYP1A2 haplotypes are critical in inducing variations in enzyme activity, with the exception of CYP1A2*1F.

CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

“…Even controlling for the effect of genotype and OC use there was no F o r P e e r R e v i e w 11 significant difference between smokers and non-smokers on enzyme activity. Among cytochrome P450 drug metabolizing enzymes that expressed in the liver, CYP1A2 is the only one whose activity is affected by smoking habit [20]. Previous studies reported interaction between smoking and CYP2C19 genotype in influencing H.Pylori eradication success and suggested interaction between smoking and CYP2C19 should be examined in the future [29].…”

“…In the Swedish subjects the mean age was 29 ± SD 8.3 years (range 18-60) with the mean weight 69 ± SD 12 kg (range 47-109) (no data on weight in two subjects). The Swedish subjects consisted of 112 women and 73 men and 39 (11 men and 28 women) were classified as smokers (definition of smokers > 2 cigarettes/ day) as described previously [19,20]. There were 44 women using OC.…”

Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome

“…35 This finding, however, may not be applicable for Caucasians due to further interethnic genetic differences as discussed previously. 19 The CYP1A2*1F (À163A) polymorphism was associated with higher clearance of the CYP1A2 substrate caffeine in Caucasian smokers 18,19 but not in nonsmokers or in Korean smokers. Despite the close concordance between caffeine and olanzapine clearance, 26,36 different characteristics in the examined study populations-steady-state olanzapine concentrations in patients vs single-dose administration in healthy volunteers-may have led to different results.…”

“…15,16 The CYP1A2*1F (À163A) polymorphism (rs762551) has been associated with higher enzyme inducibility and higher clearance of CYP1A2 substrates such as melatonin 17 or caffeine in Caucasian smokers. 18,19 We investigated whether the CYP1A2*1F polymorphism has a significant impact on olanzapine serum concentration in a clinical setting. We examined further whether this polymorphism, the olanzapine serum concentrations or pharmacodynamic polymorphisms are associated with treatment response or side effects including acute weight gain.…”

Four Polymorphisms in the Cytochrome P450 1A2 (CYP1A2) Gene and Lung Cancer Risk: a Meta-analysis

“…CYP1A2 is an important gene in catalyzing 2-and 4-hydroxylations of estrogens (Yamazaki et al, 1998;Tsuchiya et al, 2005;Nebert et al, 2006) and metabolism of carcinogens (Eaton et al, 1995;Nebert et al, 1996;Nebert et al, 2004). In humans, CYP1A2 is highly polymorphic and several single nucleotide polymorphisms (SNPs) including four common SNPs represented as CYP1A2 p.N516N (rs2470890; 1545T>C), CYP1A2*1C (rs2060514; -3858G>A), and CYP1A2*1F (rs762551; -163C>A) alleles have been identified in different ethnic population worldwide (Chida., 1999;Aklilllu et al, 2003;Ghotbi et al, 2007). CYP1A2*1C, located in the 5'-noncoding promoter region of CYP1A2, was reported to be associated with decreased enzyme inducibility in Japanese smokers but seems to be very rare (Nakajima et al, 1999).…”