Phenotype-genotype analysis of CYP1A2 in Japanese patients receiving oral theophylline therapy

Takata, Keiji; Saruwatari, Junji; Nakada, Naoyuki; Nakagawa, M.; Fukuda, Keiichi; Tanaka, Fujiho; Takenaka, Shinobu; Mihara, Shuichi; Marubayashi, Toru; Nakagawa, Kazuko

doi:10.1007/s00228-005-0057-z

Cited by 39 publications

(21 citation statements)

References 21 publications

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“…We did not find a functional effect of any of the CYP1A2 SNPs, haplotypes, or diplotypes identified, which is consistent with the previous studies [Jiang et al, 2006;Takata et al, 2006]. Other studies, however, have reported otherwise.…”

Section: Discussionsupporting

confidence: 91%

Haplotypes in the 5′‐untranslated region of the CYP1A2gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism

Gervasini

Ghotbi

Aklillu

et al. 2012

Environ and Mol Mutagen

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In this study, we analyzed the influence of CYP1A2 genetic variation and enzyme activity on lung cancer risk in a high-incidence area. A total of 95 lung cancer patients and 196 controls were genotyped for the -3860G/A, -3113A/G, -2467T/delT, -739T/G, and -163C/A polymorphisms in the 5'-untranslated region of the gene. In addition, a subset of 70 patients and 115 controls were phenotyped by high-performance liquid chromatography determination of the caffeine metabolic ratio (CMR). The -2467T/delT polymorphism and the CYP1A2*1V haplotype (-163C>A, -2467T>delT) were inversely associated with lung cancer risk (odds ratio [OR] = 0.47 [0.2-0.9]; P = 0.02 and OR = 0.13 [0.02-1.0]; P = 0.04; respectively). In addition, the CYP*1A/*1V and *1F (-163C>A)/*1D (-163C>A, -2467T>delT) diplotypes were absent in the patients group, whereas accounting for 7.1% (P = 0.017) and 5.6% (P = 0.037) of controls, respectively. Mean CMR was significantly higher in patients than in controls (10.50 ± 17.31 vs. 6.52 ± 6.26, P = 0.01) but regression analyses did not yield significant ORs for the association with lung cancer risk. Similarly, no significant correlations were found between any genetic variant and enzyme activity. Several CYP1A2 haplotypes and diplotypes containing the -2467delT variant were associated with lower lung cancer risk; however, they did not correlate with significant changes in CYP1A2 metabolic activity toward caffeine.

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Section: Discussionsupporting

confidence: 91%

Haplotypes in the 5′‐untranslated region of the CYP1A2gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism

Gervasini

Ghotbi

Aklillu

et al. 2012

Environ and Mol Mutagen

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“…Some studies found decreased enzyme activity or inducibility associated with the A allele [18], [44]. Other studies found no difference in the enzyme activities or inducibility between the G and A alleles [21], [45]. One study reported the A allele was related to increased CYP1A2 activity [46].…”

Section: Discussionmentioning

confidence: 99%

Quantitative Assessment of the Influence of Cytochrome P450 1A2 Gene Polymorphism and Colorectal Cancer Risk

et al. 2013

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Cytochrome P450 1A2 (CYP1A2) encodes a member of the cytochrome P450 superfamily of enzymes, which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of colorectal cancer (CRC). The CYP1A2*C (rs2069514) and CYP1A2*F (rs762551) polymorphism are two of the most commonly studied polymorphisms of the gene for their association with risk of CRC, but the results are conflicting. To derive a more precise estimation of the relationship between CYP1A2 and genetic risk of CRC, we performed a comprehensive meta-analysis which included 7088 cases and 7568 controls from 12 published case-control studies. In a combined analysis, the summary per-allele odds ratio for CRC was 0.91 (95% CI: 0.83–1.00, P = 0.04), and 0.91 (95% CI: 0.68–1.22, P = 0.53), for CYP1A2 *F and *C allele, respectively. In the subgroup analysis by ethnicity, significant associations were found in Asians for CYP1A2*F and CYP1A2*C, while no significant associations were detected among Caucasian populations. Similar results were also observed using dominant genetic model. Potential sources of heterogeneity were explored by subgroup analysis and meta-regression. No significant heterogeneity was detected in most of comparisons. This meta-analysis suggests that the CYP1A2 *F and *C polymorphism is a protective factor against CRC among Asians.

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“…It is not quite clear yet how much the CYP1A2*1F allele influences actual enzyme activity. When caffeine metabolites were measured, enzyme activity was higher among carriers of the CYP1A2*1F allele in one [33], but not in another report [34]. Given the stronger association of percent density with progesterone than estrogens [3,7], polymorphisms related to progestin metabolism may provide additional insights.…”

Section: Discussionmentioning

confidence: 99%

Breast density and polymorphisms in genes coding for CYP1A2 and COMT: the Multiethnic Cohort

2007

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Background: Mammographic density is a strong predictor of breast cancer risk and is increased by hormone replacement therapy (HRT). Some associations with genetic polymorphisms in enzymes involved in estrogen metabolism have been described. This cross-sectional analysis examined the relation between mammographic density and the CYP1A2*1F and COMT Val 58 Met polymorphisms among 332 breast cancer cases and 254 controls in the Hawaii component of the Multiethnic Cohort.

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Phenotype-genotype analysis of CYP1A2 in Japanese patients receiving oral theophylline therapy

Abstract: These results suggest that the CYP1A21C and CYP1A21F genotypes are not crucial factors for the variability of CYP1A2 activity and that the CYP1A2*1K haplotype is either nil or only shows a very low frequency in Japanese.

Cited by 39 publications

References 21 publications

Haplotypes in the 5′‐untranslated region of the CYP1A2gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism

Haplotypes in the 5′‐untranslated region of the CYP1A2gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism

Quantitative Assessment of the Influence of Cytochrome P450 1A2 Gene Polymorphism and Colorectal Cancer Risk

Breast density and polymorphisms in genes coding for CYP1A2 and COMT: the Multiethnic Cohort

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Phenotype-genotype analysis of CYP1A2 in Japanese patients receiving oral theophylline therapy

Abstract: These results suggest that the CYP1A2*1C and CYP1A2*1F genotypes are not crucial factors for the variability of CYP1A2 activity and that the CYP1A2*1K haplotype is either nil or only shows a very low frequency in Japanese.

Cited by 39 publications

References 21 publications

Haplotypes in the 5′‐untranslated region of the CYP1A2gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism

Haplotypes in the 5′‐untranslated region of the CYP1A2gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism

Quantitative Assessment of the Influence of Cytochrome P450 1A2 Gene Polymorphism and Colorectal Cancer Risk

Breast density and polymorphisms in genes coding for CYP1A2 and COMT: the Multiethnic Cohort

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Product

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Abstract: These results suggest that the CYP1A21C and CYP1A21F genotypes are not crucial factors for the variability of CYP1A2 activity and that the CYP1A2*1K haplotype is either nil or only shows a very low frequency in Japanese.