Genetic polymorphism of cyp1a2 but not total or free. We discovered that another snp in cyp1a2, rs2472300, is in 100% linkage disequilibrium with rs762551. Therefore, genotyping for cyp1a2 1d and 1f may be a useful tool for dose optimization and identification of highrisk patients. A strong influence of the cyp1a2 1f allele on overall leflunomide toxicity was observed, as the carriers of cyp1a2 1f cc genotype had a 9. Caffeine, cyp1a2 genotype, and endurance performance in. Cyp3a3, cyp2c18, no cases of genetic polymorphism have been observed so far 1, 3, 4, 8. This study intended to ascertain associations between cyp19a1 and cyp1a2 gene polymorphisms with the t2dm risk in chinese han. Therefore, this genetic polymorphism is a potential candidate to explain variability of ergogenic response to caffeine supplementation.
Cyp1a2 genetic polymorphisms are associated with treatment response to the antidepressant paroxetine. The aim of the present study was to test for an association between the cyp1a2. However, studies considered cyp1a2 as one of the major cyp in the liver. Sep 21, 2017 the influence of genetic cyp1a2 1f, cyp1a2 1c and cyp2c192 and nongenetic parameters age, weight, gender, tobacco, coffee, and alcohol consumption on the variation of the clz c0d ratio was. Research open access association of cyp19a1 and cyp1a2. The rs762551 polymorphism in the cyp1a2 gene was initially used to identify fast and slow metabolizers of caffeine. Cyp1a2 accounts for 95% of caffeine metabolism and. Cyp1a2 genetic polymorphisms are associated with treatment. Pdf genetic polymorphism of cyp1a2 and the toxicity of.
Genetic polymorphisms have the same ethnicity as racial differences 3,22,23. Nov 19, 2012 genetic polymorphism rs762551ac in gene encoding cytochrome p450 1a2 cyp1a2 has been shown to influence the inducibility of cyp1a2 expression and thus might be associated with risk of several types of human cancer. Mar 17, 2007 to investigate the cyp1a2 genotypephenotype relationship and to compare cyp1a2 genetic polymorphisms and enzyme activity in terms of the effect of smoking and oral contraceptive oc use in swedes and koreans. Cytochrome p450 polymorphism n molecular, metabolic, and. Background cytochrome p450 1a2 gene cyp1a2 polymorphisms have been suggested to be associated with increased side effects to antipsychotics. However, other genes such as cyp1a2 and cyp2b11 control the protein syntheses involved in the metabolism of many drugs. Genetic polymorphisms of cytochrome p4501a2 cyp1a2 among emiratis mohammad m. Cyp1a2 activity was determined from the paraxanthine.
Paroxetine is a drug of choice in the treatment of major depressive disorder mdd. Its metabolism has recently been reported to be mediated through the cyp enzymes 1a2 and 2d6. Pdf comparisons of cyp1a2 genetic polymorphisms, enzyme. Polymorphisms in the cytochrome p450 cyp1a2 gene cyp1a2 in. The effect of cyp1a2 gene polymorphism on the metabolism of. Genetic susceptibility to tardive dyskinesia in chronic. In the present study, the mdr1, cyp1a2 and cyp2b11 genes were examined to identify snp polymorphisms. Investigation of the influence of cyp1a2 and cyp2c19. Research article open access the influence of a cyp1a2. Inducibility of cyp1a2 by omeprazole in vivo related to. Studies reporting the pharmacokinetic parameters of cyp1a2. Recently, genetic variants of the cyp1a2 rs2069514 gene in the etiology of several cancers have drawn increasing attention.
Type 2 diabetes mellitus t2dm, one of the global health issues, is a group of metabolic diseases and is affected by several genetic loci in the clinical phenotype. The aim of this study was to investigate whether genetic polymorphisms in cyp1a2 and. Association of cyp19a1 and cyp1a2 genetic polymorphisms with. Pdf cytochrome p450 1a2 cyp1a2 is one of the cyp450 mixedfunction oxidase system that is of clinical importance due to the large number of drug. The association of genetic polymorphisms in cyp1a2. Pdf the cyp1a2 163ca polymorphism does not alter the. The cytochrome p450 cyp1a2 genetic polymorphisms 1f and 1d. Cyp1a21f polymorphism decreases clinical response to. Nov 01, 2012 cyp1a2 activity is also modulated by specific polymorphisms in the cyp1a2 gene 1621.
May 18, 2011 we aimed to determine the interindividual change in cyp1a2 activity after smoking cessation and to relate it to cyp1a2 genetic polymorphisms. Association of cyp1a1, cyp1a2, gstm1 and nat2 gene. Cytochromes p450, mainly cyp1a2 and cyp2c19, may be involved in the transformation of leflunomide to leflunomide metabolite a77 1726, 2cyano3hydroxy n 4trifluoromethylphenyl2butenamide. Pdf genetic susceptibility to tardive dyskinesia in. Original article genetic polymorphism of cyp1a2 increases the. Genetic polymorphisms of cytochrome p4501a2 cyp1a2 among. The cyp1a2 1f rs762551 polymorphism was detected using either of two. Breast density and polymorphisms in genes coding for cyp1a2. Pdf to investigate the cyp1a2 genotypephenotype relationship and to compare cyp1a2 genetic polymorphisms and enzyme activity in.
Pmid 23175176 variation in pahrelated dna adduct levels among nonsmokers. Impact of cyp1a2 genetic polymorphisms on pharmacokinetics of. The cytochrome p450 cyp1a2 genetic polymorphisms 1f and. Among the genetic variations that have been investigated in dogs, the multidrug resistance gene mdr is the best studied.
Flockhart, in clinical and translational science second edition, 2017. Cytochrome p450 1a2 gene cyp1a2 polymorphisms have been suggested to be associated with increased side effects to antipsychotics. Environmental and genetic factors are shown to influence the activity of cyp1a2. Genetic polymorphism of cyp1a2 but not total or free teri. L reaction contained 100 ng genomic dna, 10 mmoll tris hcl, 1. The cyp1a2 1f polymorphism is located in a noncoding region of the gene, but may result in differential binding of regulatory proteins to the surrounding sequence and alter cyp1a2 expression levels. Genetic polymorphisms of the cyp3a4, cyp3a5, cyp3a7 and. Association between common cyp1a2 polymorphisms and. Genetic polymorphism of the adenosine a2a receptor is. Cyp1a2 rs2069514 polymorphism and lung cancer susceptibility. Compared to patients who were homozygous for the major allele in both genes cyp1a2 aa and ahr gg, a 9fold risk for early events was found in. Moreover, a related study on cyp450 activities proved that the activity of cyp1a2 is slightly increased in the subjects with diabetes 20.
In our current study, we tested whether genetic polymorphisms in cyp1a2 are associated with the treatment efficacy and side effects of paroxetine. Pdf paroxetine is a drug of choice in the treatment of major depressive disorder mdd. The purpose of the present study was to determine if this specific cyp1a2 polymorphism influences the ergogenic effect of caffeine supplementation in trained cyclists. Saliva samples were analyzed to determine the genotype of each player for the. Genetic polymorphism of cyp1a2 increases the risk of. Single nucleotide polymorphisms snps in cyp1a1 and cyp1a2 are. Research article genetic polymorphisms of cytochrome p4501a2 cyp1a2 among emiratis mohammad m. Our data suggest that caffeineinduced impairments in postprandial glycaemia are related to 1976t c and. Mar 10, 2003 sofia pavanello, alessandra pulliero, silvia lupi, pasquale gregorio, erminio clonfero, influence of the genetic polymorphism in the 5. Genetic polymorphisms of cytochrome p4501a2 cyp1a2. We, for the first time, identified a significant influence of polymorphisms in cyp1a2 in combination with cyp1a2 inducer status on the clinical outcome. Impact of cyp1a2 genetic polymorphisms on pharmacokinetics.
Bastaki1 1 department of pharmacology, college of medicine and health sciences, uae university, al ain, abu. Several single nucleotide polymorphisms snps of the cytochrome p450 enzyme 1a2 gene cyp1a2 have been reported. Pdf genetic polymorphisms of cytochrome p4501a2 cyp1a2. Individuals who are homozygous for the high inducibility. Cyp1a2 genetic polymorphism is associated with treatment. A single nucleotide polymorphism in the dog cyp1a2 gene causes these animals to be cyp1a2 deficient i. Association of cyp19a1 and cyp1a2 genetic polymorphisms. It was concluded that the cyp1a2 gene could be a contributing factor to prevent early ageing from occupational exposure. Pdf cyp1a2 genetic polymorphisms are associated with.
However, only two of these snps namely cyp1a2 1c g4a and cyp1a2 1f c4a have been shown to be of functional significance. Cyp 1a1, cyp1a2, and cyp2e1 genes modulate susceptibility to gastric cancer in patients with helicobacter. Genetic polymorphisms of cytochrome p450 cyp 1a2 allele. Genotyping of four genetic polymorphisms in the cyp1a2. Cyp1a2 functions primarily to metabolize several antipsychotic medications and theophylline. To determine the impact of cyp1a2 genetic polymorphisms on the pharmacokinetics of cyp1a2. Bastaki1 1 department of pharmacology, college of medicine and health sciences, uae university, al ain, abu dhabi, united arab emirates, 2 department of. Cyp1a21d and 1f polymorphisms have a significant impact on. We studied the association of response to clozapine treatment in schizophrenic patients in relation to polymorphisms in the cyp1a2 gene. The effects of drugs are individualized and strongly influenced by genetic, one of which is cyp1a2 gene polymorphisms. Nevertheless, several studies have implicated cyp1a2 gene polymorphisms in cancer susceptibility 9,10 and other diseases 11.
Another single nucleotide polymorphism was found in intron 1, which is associated with high catalytic activity when subjects are exposed to tobacco smoke 46, 47. This study aimed to determine the profile of cyp1a2 polymorphism and theophylline level in asthma exacerbation patients receiving. Genetic polymorphisms of individual drugmetabolizing genes cyp1a2. The primers indicated as r1 and r3 in the figure were used for pcr, and the amplified dna fragments were sequenced as described in materials and methods. However, studies on this are scarce and have been conducted with either various antipsychotics or only in small samples of patients receiving clozapine. Comparisons of cyp1a2 genetic polymorphisms, enzyme activity and the genotypephenotype relationship in swedes and koreans.
Genetic polymorphisms in adora2a and cyp1a2 influence. A systematic search was conducted in pubmed and scopus databases as of june 26, 2018. Role of cyp1a2 polymorphisms in breast cancer risk in women. The effect of cyp1a2 gene polymorphism on the metabolism. To we knowledge, this metaanalysis is firstly available for comprehensively evaluating the associations between cyp1a2 rs2069514 polymorphism and lung cancer risk.
Found in close linkage with cyp1a1 gene as they shared a common 5flanking. The impact of the cyp1a2 rs762551 callele was modified by a functional polymorphism in the regulator gene ahr arg554lys ga. Feb 18, 2020 the present study is the first, to the best of our knowledge, to analyze the association of polymorphisms in cyp1a2, ugt1a4, and abcb1. Influence of the genetic polymorphism in the 5noncoding region of the cyp1a2 gene on cyp1a2 phenotype and urinary mutagenicity in smokers. The influence of a cyp1a2 polymorphism on the ergogenic. The genetic polymorphism of cyp isoenzymes participating in drug biotransformation is presented in table 1. Gene polymorphism colorectal cancer cyp1a1 cyp1a2 gstm1 nat2. Cyp1a2 rs762551 polymorphism contributes to cancer. In the case of some cyp isoenzymes involved in drug biotransformation, e. The impact of genetic polymorphisms on cyp1a2 activity in.
Four polymorphisms cyp1a2 1c g3860a, g31a, cyp1a2 1f c163a and cyp1a2 1b c5347t were screened in 238 unrelated male volunteers. Association of cyp19a1 and cyp1a2 genetic polymorphisms with type 2 diabetes mellitus risk in the chinese han population yafeng yang1 and ping wang2 abstract background. Cytochromes p450, mainly cyp1a2 and cyp2c19 might be involved in the transformation of leflunomide to leflunomide metabolite a77 1726. Genetic polymorphism of cyp1a2 increases the risk of myocardial. Cyp1a2, gstm1, and gstt1 polymorphisms and diet effects on.
Frequencies of cyp1a2 single nucleotide polymorphism in. Cytochrome p450 1a2 cyp1a2 is one of the cyp450 mixedfunction oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. The influence of genetic cyp1a2 1f, cyp1a2 1c and cyp2c192 and nongenetic parameters age, weight, gender, tobacco, coffee, and alcohol consumption on the variation of the clz c0d ratio was. Cyp1a2 genetic polymorphisms influenced cyp1a2 enzyme activity as measured by caffeine, but cyp1a2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study. Comparisons of cyp1a2 genetic polymorphisms, enzyme activity. However, the results of previous studies on the associations of this polymorphism with risk of cancer are not all consistent. Genetic polymorphism of cyp1a2 in ethiophians affecting induction and expression. Genetic polymorphism of cytochrome p450 cyp 1a1, cyp1a2. Genetic polymorphism of cyp genes, alone or in combination.
Influence of the genetic polymorphism in the 5noncoding region of the cyp1a2 gene on cyp1a2 phenotype and urinary mutagenicity in. Cyp1a2 1f has recently been associated with increased cyp1a2 inducibility 6. Aug 19, 2020 genetic polymorphisms of cyp1a2 have been extensively studied in a variety of populations, and were found to be involved in the etiology of developing cancers and other diseases, 16,17,18,19. These can account for up to a 60fold difference in activity. Aminophylline theophylline is one of the most frequent asthma therapies in indonesia, although it remains as a narrow therapy. Snp genetic polymorphisms of mdr1, cyp1a2 and cypb11 genes. The aim of this study was to investigate if genetic polymorphisms in cyp1a2 and cyp2c19 influence leflunomide pharmacokinetics, treatment response and the occurrence of. The association of genetic polymorphisms in cyp1a2, ugt1a4. Genetic polymorphism of cyp1a2 in ethiopians affecting. Dmd 27482 investigation of the influence of and cyp2c19. Cyp1a2 in the liver through an initial n3demethylation 16, 17.
The cyp1a2 1f polymorphism was analyzed using a pcrrestriction fragment length polymorphism method. Polymorphisms in the cyp1a2 genes have the potential to affect the individual capacity to convert precarcinogens into carcinogens. Inducibility of cyp1a2 by omeprazole in vivo related to the. Cyp1a2 gene polymorphism and theophylline level in asthma. Cyp1a2 is one of the drugmetabolizing enzymes of major importance, as it catalyzes the phase i. Caffeine intake, cyp1a2 polymorphism and the risk of.
With these comprehensive metaanalyses, we aimed to provide a quantitative assessment of the association between the published genetic association studies on cyp1a2 single nucleotide polymorphisms snps and the risk of cancer. Furthermore, polymorphisms in cyp2c19 have been associated with altered plasma concentration, but to date no association of concentration with cyp1a2 genotype or smoking has been seen. The genetic polymorphism may only affect postmenopausal women with low body fat, low endogenous estrogens, and relatively low cyp1a2 activity, whereas the higher estrogen levels and cyp1a2 activity in women who use hrt, will develop breast cancer, or are overweight may outweigh any changes in hormone patterns due to the cyp1a2 variant alleles. The aim of this investigation was to analyze the influence of the genetic variations of the 163ca polymorphism of the cyp1a2 gene on. Cyp1a2 polymorphism has been well studied in white persons and asians but not in africans. Inducibility of cyp1a2 by omeprazole in vivo related to the genetic polymorphism of cyp1a2.
This study was designed to investigate the impact of cytochrome p450 cyp 1a2 polymorphisms on theophylline metabolism in a nonsmoking healthy male chinese population. Breast density and polymorphisms in genes coding for. We performed cyp1a2 genotype and phenotype analysis using caffeine in ethiopians living in ethiopia n 100 or in sweden n 73. The primers indicated as r1 and r3 in the figure were used for pcr, and the amplified dna fragments were sequenced as. Alahmad1, naheed amir1, subramanian dhanasekaran1, anne john2, yousef m.
An increased tardive dyskinesia severity was variation in the expression and activity of cyp1a2 observed in patients with the a allele of the cyp1a2 1c suggests a role for genetic factors in its control such as polymorphism and in another study with cyp1a2 ca single nucleotide polymorphisms, as well as epigenetic 9,10, while the cyp1a2. Theophylline has been used in the treatment of asthma patients. Genetic polymorphisms of cytochrome p450 cyp may predict the treatment response or occurrence of side effects of antipsychotic drugs. This study aimed to determine the profile of cyp1a2 polymorphism and theophylline level in asthma exacerbation patients receiving intravenous aminophylline therapy. This thesis is focused on the cyp1a2 gene and its expression, and factors that may affect its regulation and activity to further explain the variation in enzyme activity, as well as the effect of genetic polymorphisms in the cyp1a2, mdr1 and ugt1a4 genes on the metabolism of the antipsychotic drug olanzapine. Dec 27, 2017 genetic polymorphism of cyp1a2 in ethiopians affecting induction and expression. Association of cyp2d6 and cyp1a2 gene polymorphism with. In addition, significant interindividual differences in the elimination of drugs metabolized by cyp1a2 enzyme have been observed which are largely due to the highly polymorphic nature of cyp1a2. We sequenced the cyp1a2 gene using genomic dna from 12 subjects, which revealed a novel intron 1 singlenucleotide polymorphism snp, 730ct. Leflunomide is a diseasemodifying antirheumatic drug used for the treatment of rheumatoid arthritis ra. Genotyping a colony of 79 dogs revealed 77% wildtype, 19% heterozygous, and 4% homozygous mutant animals. Genotyping of four genetic polymorphisms in the cyp1a2 gene.
This study suggests that cyp1a2 genetic polymorphisms have no significant. Cyp1a2 enzyme activity was determined in 194 and 150 healthy swedish and korean subjects, respectively, on the basis of the 4h plasma paraxanthinecaffeine 17x7x ratio determined. Comparisons of cyp1a2 genetic polymorphisms, enzyme activity and the genotypephenotype relationship in. A total of 241 mdd patients who had taken paroxetine continually for 8 weeks were recruited, and their steady state paroxetine concentrations were measured at weeks 2, 4 and 8.
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