Five novel natural allelic variants?951A&gt;C, 1042G&gt;A (D348N), 1156A&gt;T (I386F), 1217G&gt;A (C406Y) and 1291C&gt;T (C431Y)?of the human CYP1A2 gene in a French Caucasian population

Chevalier, Dany; Cauffiez, Christelle; Allorge, Delphine; Lo-Guidice, Jean-Marc; Lhermitte, Michel; Lafitte, Jean-Jacques; Broly, Franck

doi:10.1002/humu.49

Cited by 29 publications

(22 citation statements)

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“…The frequency of the CYP1A2 ‐164A→C polymorphism ( CYP1A2 * 1F , 33.3%) was comparable to that found in an earlier study in German Caucasians (32.2%) [18]. In a recent report, CYP1A2 1545T→C ( CYP1A2 * 1B , * 1G , * 1H and * 3 ) was found to be present in 70 of 200 French Caucasian chromosomes (35.0%) [26], which compares well with the CYP1A2 ‐1545T→C frequency of 38.2% found in the present study. Polymorphisms CYP1A2 ‐2464T→delT ( CYP1A2 * 1D ) and CYP1A2 740T→G ( CYP1A2 * 1E and * 1G ) were significantly less frequent in our 114 Caucasians (frequency 4.82% and 0.44% of chromosomes, respectively) than in 159 Japanese individuals (42.0% and 8.20%) [15].…”

Section: Discussionsupporting

confidence: 70%

Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism

Sachse

Bhambra

Smith

et al. 2003

Brit J Clinical Pharma

158

106

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Aims Several single nucleotide polymorphisms (SNPs) of the cytochrome P450 enzyme 1A2 gene ( CYP1A2 ) have been reported. Here, frequencies, linkage disequilibrium and phenotypic consequences of six SNPs are described. Methods From genomic DNA, 114 British Caucasians (49 colorectal cancer cases and 65 controls) were genotyped for the CYP1A2 polymorphisms -, and 1545T AE C (alleles CYP1A2 * 1B , * 1G , * 1H and * 3 ), using polymerase chain reaction-restriction fragment length polymorphism assays. All patients and controls were phenotyped for CYP1A2 by h.p.l.c. analysis of urinary caffeine metabolites. Results In 114 samples, the most frequent CYP1A2 SNPs were 1545T AE C (38.2% of tested chromosomes), -164A AE C ( CYP1A2 * 1F , 33.3%) and -2464T AE delT ( CYP1A2 * 1D , 4.82%). The SNPs were in linkage disequilibrium: the most frequent constellations were found to be -3858G/ -2464T/ -740T/ -164A/63C/1545T (61.8%), -3858G/ -2464T/ -740T/ -164C/63C/1545C (33.3%), and -3858G/ -2464delT/ -740T/ -164A/63C/1545C (3.51%), with no significant frequency differences between cases and controls. In the phenotype analysis, lower caffeine metabolic ratios were detected in cases than in controls. This was significant in smokers ( n = 14, P = 0.020), and in a subgroup of 15 matched case-control pairs ( P = 0.007), but it was not significant in nonsmokers ( n = 100, P = 0.39). There was no detectable association between CYP1A2 genotype and caffeine phenotype. Conclusions (i) CYP1A2 polymorphisms are in linkage disequilibrium. Therefore, only -164A AE C ( CYP1A2 * 1F ) and -2464T AE delT ( CYP1A2 * 1D ) need to be analysed in the routine assessment of CYP1A2 genotype; (ii) in vivo CYP1A2 activity is lower in colorectal cancer patients than in controls, and (iii) CYP1A2 genotype had no effect on phenotype (based on the caffeine metabolite ratio). However, this remains to be confirmed in a larger study.

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Section: Discussionsupporting

confidence: 70%

Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism

Sachse

Bhambra

Smith

et al. 2003

Brit J Clinical Pharma

158

106

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“…Therefore, we individually expressed different CYP1A2 polymorphisms in budding yeast, which does not contain P450 enzymes that activate aflatoxins. We studied the rare polymorphisms C406Y, D348N, and I386F, first found in the French population [34]. To determine whether expression of specific P450 alleles conferred differences in the metabolic activation of AFB 1 , we measured AFB 1 -associated DNA adducts, recombination frequencies, survival of a AFB 1 -sensitive DNA repair mutant and Rad51 foci formation.…”

Section: Discussionmentioning

confidence: 99%

“…CYP1A2*1F , the intron 1 polymorphism −163C > A located downstream of the untranslated first exon, is associated with pancreatic cancer among heavy smokers [31], with squamous cell lung carcinoma, and with colorectal adenomas [32,33]. Even less is known about the rare polymorphisms that are found in coding sequences, such as those originally found in the French [34] and Japanese populations [35]. Thus, additional methods, besides epidemiological, are required to ascertain the functional significance of CYP1A2 alleles.…”

Section: Introductionmentioning

confidence: 99%

Activation of aflatoxin B1 by expression of human CYP1A2 polymorphisms in Saccharomyces cerevisiae

Fasullo

Smith

Egner

et al. 2014

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Human susceptibility to environmental carcinogens is highly variable and depends on multiple genetic factors, including polymorphisms in cytochrome P450 genes. Although epidemiological studies have identified individual polymorphisms in cytochrome P450 genes that may alter cancer risk, there is often conflicting data about whether such polymorphisms alter the genotoxicity of environmental carcinogens. This is particularly true of the CYP1A2 polymorphisms that confer differential activation of multiple human carcinogens. To determine whether a single cytochrome P450 polymorphism confers higher levels of carcinogen-associated genotoxicity, we chose an organism that lack enzymes to metabolically activate aflatoxins and expressed individual human P450 genes in budding yeast. We measured the frequencies of recombination, Rad51 foci formation, 7-methoxyresorufin O-demethylase, and the concentrations of carcinogen-associated DNA adducts in DNA repair proficient yeast expressing P450 polymorphisms after exposure to aflatoxin B1 (AFB1). We measured growth of rad4 rad51 cells expressing CYP1A2 polymorphisms while exposed to AFB1. We observed that there was significantly less AFB1-associated genotoxicity in yeast expressing I386F, while yeast expressing CYP1A2 C406Y exhibited intermediate levels of genotoxicity compared to yeast expressing CYP1A2 D348N or wild type. We conclude that differences in carcinogen genotoxicity can be observed in yeast expressing different CYP1A2 alleles. This is the first report that carcinogen-associated P450 polymorphisms can be studied in yeast.

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“…paraxanthine (81.5%) (Campbell, Grant, Inaba, & Kalow, 1987;Gu, Gonzalez, Kalow, & Tang, 1992;Tassaneeyakul et al, 1994), by cytochrome P-450 enzymes, in particular the P-450 1A2, which is coded by the gene CYP1A2 (Lelo, Birkett, Robson, & Miners, 1986;Miners & Birkett, 1996). An A to C substitution at position À163 (rs762551) in the CYP1A2 gene may explain inter-individual variation in caffeine metabolism rate (Aklillu et al, 2003;Chevalier et al, 2001;Grosso & Bracken, 2005;Han et al, 2001;Nakajima et al, 1999;Sachse, Brockmoller, Bauer, & Roots, 1999;Sachse et al, 2003;Signorello et al, 2001). Carriers of the À163C allele can be considered slow caffeine metabolizers, whereas homozygous for the À163A allele are more rapid caffeine metabolizers (Cornelis, El-Sohemy, & Campos, 2007;Sachse et al, 1999).…”

Section: Introductionmentioning

confidence: 96%

Caffeine metabolism rate influences coffee perception, preferences and intake

Masi

Dinnella

Pirastu

et al. 2016

Food Quality and Preference

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Five novel natural allelic variants?951A>C, 1042G>A (D348N), 1156A>T (I386F), 1217G>A (C406Y) and 1291C>T (C431Y)?of the human CYP1A2 gene in a French Caucasian population

Cited by 29 publications

References 5 publications

Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism

Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism

Activation of aflatoxin B1 by expression of human CYP1A2 polymorphisms in Saccharomyces cerevisiae

Caffeine metabolism rate influences coffee perception, preferences and intake

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