Influence of the genetic polymorphism in the 5′-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers
The functional significance of genetic polymorphisms on tobacco smoke-induced CYP1A2 activity was examined. The influence of three polymorphisms of the cytochrome P450 1A2 gene ( CYP1A2) (− 3860 G → A (allele *1C), − 2467 T → delT (allele *1D), − 163 C → A (allele *1F)), located in the 5′-noncoding...
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| Veröffentlicht in: | Mutation research 2005-11, Vol.587 (1), p.59-66 |
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| creator | Pavanello, Sofia Pulliero, Alessandra Lupi, Silvia Gregorio, Pasquale Clonfero, Erminio |
| description | The functional significance of genetic polymorphisms on tobacco smoke-induced CYP1A2 activity was examined. The influence of three polymorphisms of the cytochrome P450 1A2 gene (
CYP1A2) (−
3860 G
→
A (allele
*1C), −
2467 T
→
delT (allele
*1D), −
163
C
→
A (allele
*1F)), located in the 5′-noncoding promoter region of the gene, on CYP1A2 activity (measured as caffeine metabolic ratio, CMR), was studied in Caucasian current smokers (
n
=
95). Tobacco smoke intake was calculated from the number of cigarettes/day. Also, studied was the influence of these
CYP1A2 genotypes on smoking-associated urinary mutagenicity, detected in
Salmonella typhimurium strain YG1024 with S9 mix, considering the urinary excretion of nicotine plus its metabolites as an internal indicator of tobacco smoke exposure.
Smokers with at least one of the variant alleles
CYP1A2 −
3860A and −
2467 delT showed a significantly increased CYP1A2 CMR (−
3860 G/A versus
G/G,
p
<
0.05; −
2467 delT/delT versus
T/delT and
T/T,
p
<
0.01). Multiple regression analysis showed that the increase in CYP1A2 CMR (ln values) was again significantly related to the presence of
CYP1A2 variants −
2467delT and also to variant −
163A (
p
<
0.05), but moderately to −
3860A (
p
=
0.084). No influence of the number of cigarettes smoked per day by each subject was found. Heavy smokers (
n
=
48, with urinary nicotine plus its metabolites
≥0.69
mg/mmol creatinine) with variant allele −
2467delT or −
163A had significantly increased urinary mutagenicity (
p
<
0.01 and |
| doi_str_mv | 10.1016/j.mrgentox.2005.08.008 |
| format | Article |
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CYP1A2) (−
3860 G
→
A (allele
*1C), −
2467 T
→
delT (allele
*1D), −
163
C
→
A (allele
*1F)), located in the 5′-noncoding promoter region of the gene, on CYP1A2 activity (measured as caffeine metabolic ratio, CMR), was studied in Caucasian current smokers (
n
=
95). Tobacco smoke intake was calculated from the number of cigarettes/day. Also, studied was the influence of these
CYP1A2 genotypes on smoking-associated urinary mutagenicity, detected in
Salmonella typhimurium strain YG1024 with S9 mix, considering the urinary excretion of nicotine plus its metabolites as an internal indicator of tobacco smoke exposure.
Smokers with at least one of the variant alleles
CYP1A2 −
3860A and −
2467 delT showed a significantly increased CYP1A2 CMR (−
3860 G/A versus
G/G,
p
<
0.05; −
2467 delT/delT versus
T/delT and
T/T,
p
<
0.01). Multiple regression analysis showed that the increase in CYP1A2 CMR (ln values) was again significantly related to the presence of
CYP1A2 variants −
2467delT and also to variant −
163A (
p
<
0.05), but moderately to −
3860A (
p
=
0.084). No influence of the number of cigarettes smoked per day by each subject was found. Heavy smokers (
n
=
48, with urinary nicotine plus its metabolites
≥0.69
mg/mmol creatinine) with variant allele −
2467delT or −
163A had significantly increased urinary mutagenicity (
p
<
0.01 and <0.05).
CYP1A2 genetic polymorphisms are shown to influence the CYP1A2 phenotype in smokers, −
2467 T
→
delT having the main effect
. This information is of interest for future studies assessing the possible role of tobacco smoke-inducible
CYP1A2 genotypes as individual susceptibility factors in exposure to carcinogens.</description><identifier>ISSN: 1383-5718</identifier><identifier>ISSN: 0027-5107</identifier><identifier>EISSN: 1879-3592</identifier><identifier>DOI: 10.1016/j.mrgentox.2005.08.008</identifier><identifier>PMID: 16188490</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Adolescent ; Adult ; Aged ; Biological and medical sciences ; Caffeine test ; CYP1A2 genotype ; CYP1A2 phenotype ; Cytochrome P-450 CYP1A2 - genetics ; Cytochrome P-450 CYP1A2 - metabolism ; Female ; Fundamental and applied biological sciences. Psychology ; Genetics of eukaryotes. Biological and molecular evolution ; Genotype ; Humans ; Individual susceptibility ; Male ; Medical sciences ; Middle Aged ; Phenotype ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Salmonella typhimurium ; Smoking - adverse effects ; Smoking - genetics ; Tobacco smoke exposure ; Tobacco smoke-induced CYP1A2 activity ; Tobacco, tobacco smoking ; Toxicology ; Urinary mutagenicity</subject><ispartof>Mutation research, 2005-11, Vol.587 (1), p.59-66</ispartof><rights>2005</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-457dd368fadfe3f1be555a21537ad5bdba2e9a5845aa31d5ad2295fd9e436a93</citedby><cites>FETCH-LOGICAL-c493t-457dd368fadfe3f1be555a21537ad5bdba2e9a5845aa31d5ad2295fd9e436a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1383571805002172$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17229543$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16188490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pavanello, Sofia</creatorcontrib><creatorcontrib>Pulliero, Alessandra</creatorcontrib><creatorcontrib>Lupi, Silvia</creatorcontrib><creatorcontrib>Gregorio, Pasquale</creatorcontrib><creatorcontrib>Clonfero, Erminio</creatorcontrib><title>Influence of the genetic polymorphism in the 5′-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers</title><title>Mutation research</title><addtitle>Mutat Res</addtitle><description>The functional significance of genetic polymorphisms on tobacco smoke-induced CYP1A2 activity was examined. The influence of three polymorphisms of the cytochrome P450 1A2 gene (
CYP1A2) (−
3860 G
→
A (allele
*1C), −
2467 T
→
delT (allele
*1D), −
163
C
→
A (allele
*1F)), located in the 5′-noncoding promoter region of the gene, on CYP1A2 activity (measured as caffeine metabolic ratio, CMR), was studied in Caucasian current smokers (
n
=
95). Tobacco smoke intake was calculated from the number of cigarettes/day. Also, studied was the influence of these
CYP1A2 genotypes on smoking-associated urinary mutagenicity, detected in
Salmonella typhimurium strain YG1024 with S9 mix, considering the urinary excretion of nicotine plus its metabolites as an internal indicator of tobacco smoke exposure.
Smokers with at least one of the variant alleles
CYP1A2 −
3860A and −
2467 delT showed a significantly increased CYP1A2 CMR (−
3860 G/A versus
G/G,
p
<
0.05; −
2467 delT/delT versus
T/delT and
T/T,
p
<
0.01). Multiple regression analysis showed that the increase in CYP1A2 CMR (ln values) was again significantly related to the presence of
CYP1A2 variants −
2467delT and also to variant −
163A (
p
<
0.05), but moderately to −
3860A (
p
=
0.084). No influence of the number of cigarettes smoked per day by each subject was found. Heavy smokers (
n
=
48, with urinary nicotine plus its metabolites
≥0.69
mg/mmol creatinine) with variant allele −
2467delT or −
163A had significantly increased urinary mutagenicity (
p
<
0.01 and <0.05).
CYP1A2 genetic polymorphisms are shown to influence the CYP1A2 phenotype in smokers, −
2467 T
→
delT having the main effect
. This information is of interest for future studies assessing the possible role of tobacco smoke-inducible
CYP1A2 genotypes as individual susceptibility factors in exposure to carcinogens.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Caffeine test</subject><subject>CYP1A2 genotype</subject><subject>CYP1A2 phenotype</subject><subject>Cytochrome P-450 CYP1A2 - genetics</subject><subject>Cytochrome P-450 CYP1A2 - metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genotype</subject><subject>Humans</subject><subject>Individual susceptibility</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Phenotype</subject><subject>Polymorphism, Genetic</subject><subject>Promoter Regions, Genetic</subject><subject>Salmonella typhimurium</subject><subject>Smoking - adverse effects</subject><subject>Smoking - genetics</subject><subject>Tobacco smoke exposure</subject><subject>Tobacco smoke-induced CYP1A2 activity</subject><subject>Tobacco, tobacco smoking</subject><subject>Toxicology</subject><subject>Urinary mutagenicity</subject><issn>1383-5718</issn><issn>0027-5107</issn><issn>1879-3592</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1DAUhiMEoqXwCpU3sEvqS5w4O6oRl0qVyqIbVpbHPpnxkNjBdhCz4wV4GR6JJ8HppOqSlW_f_5_j8xfFJcEVwaS5OlRj2IFL_mdFMeYVFhXG4llxTkTblYx39HneM8FK3hJxVryK8YAxxQyLl8UZaYgQdYfPi983rh9mcBqQ71HaA8qukKxGkx-Oow_T3sYRWffwxv_--lM677Q31u1QgJ317lG4-fqFXNMHPcq363Hag_PpOAFSzqA5WKfCEY1zUhm02qbjYh5H_w1CfF286NUQ4c26XhT3Hz_cbz6Xt3efbjbXt6WuO5bKmrfGsEb0yvTAerIFzrmihLNWGb41W0WhU1zUXClGDFeG0o73poOaNapjF8W7k-0U_PcZYpKjjRqGQTnwc5QUE0raus5gcwJ18DEG6OUU7Jg_IAmWSw7yIB9zkEsOEguZc8jCy7XCvB3BPMnWwWfg7QqoqNXQB-W0jU9cu3Rcs8y9P3GQx_HDQpBR2yUuYwPoJI23_-vlH1DTrRA</recordid><startdate>20051110</startdate><enddate>20051110</enddate><creator>Pavanello, Sofia</creator><creator>Pulliero, Alessandra</creator><creator>Lupi, Silvia</creator><creator>Gregorio, Pasquale</creator><creator>Clonfero, Erminio</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20051110</creationdate><title>Influence of the genetic polymorphism in the 5′-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers</title><author>Pavanello, Sofia ; Pulliero, Alessandra ; Lupi, Silvia ; Gregorio, Pasquale ; Clonfero, Erminio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-457dd368fadfe3f1be555a21537ad5bdba2e9a5845aa31d5ad2295fd9e436a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Caffeine test</topic><topic>CYP1A2 genotype</topic><topic>CYP1A2 phenotype</topic><topic>Cytochrome P-450 CYP1A2 - genetics</topic><topic>Cytochrome P-450 CYP1A2 - metabolism</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genotype</topic><topic>Humans</topic><topic>Individual susceptibility</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Phenotype</topic><topic>Polymorphism, Genetic</topic><topic>Promoter Regions, Genetic</topic><topic>Salmonella typhimurium</topic><topic>Smoking - adverse effects</topic><topic>Smoking - genetics</topic><topic>Tobacco smoke exposure</topic><topic>Tobacco smoke-induced CYP1A2 activity</topic><topic>Tobacco, tobacco smoking</topic><topic>Toxicology</topic><topic>Urinary mutagenicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pavanello, Sofia</creatorcontrib><creatorcontrib>Pulliero, Alessandra</creatorcontrib><creatorcontrib>Lupi, Silvia</creatorcontrib><creatorcontrib>Gregorio, Pasquale</creatorcontrib><creatorcontrib>Clonfero, Erminio</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Mutation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pavanello, Sofia</au><au>Pulliero, Alessandra</au><au>Lupi, Silvia</au><au>Gregorio, Pasquale</au><au>Clonfero, Erminio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of the genetic polymorphism in the 5′-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers</atitle><jtitle>Mutation research</jtitle><addtitle>Mutat Res</addtitle><date>2005-11-10</date><risdate>2005</risdate><volume>587</volume><issue>1</issue><spage>59</spage><epage>66</epage><pages>59-66</pages><issn>1383-5718</issn><issn>0027-5107</issn><eissn>1879-3592</eissn><abstract>The functional significance of genetic polymorphisms on tobacco smoke-induced CYP1A2 activity was examined. The influence of three polymorphisms of the cytochrome P450 1A2 gene (
CYP1A2) (−
3860 G
→
A (allele
*1C), −
2467 T
→
delT (allele
*1D), −
163
C
→
A (allele
*1F)), located in the 5′-noncoding promoter region of the gene, on CYP1A2 activity (measured as caffeine metabolic ratio, CMR), was studied in Caucasian current smokers (
n
=
95). Tobacco smoke intake was calculated from the number of cigarettes/day. Also, studied was the influence of these
CYP1A2 genotypes on smoking-associated urinary mutagenicity, detected in
Salmonella typhimurium strain YG1024 with S9 mix, considering the urinary excretion of nicotine plus its metabolites as an internal indicator of tobacco smoke exposure.
Smokers with at least one of the variant alleles
CYP1A2 −
3860A and −
2467 delT showed a significantly increased CYP1A2 CMR (−
3860 G/A versus
G/G,
p
<
0.05; −
2467 delT/delT versus
T/delT and
T/T,
p
<
0.01). Multiple regression analysis showed that the increase in CYP1A2 CMR (ln values) was again significantly related to the presence of
CYP1A2 variants −
2467delT and also to variant −
163A (
p
<
0.05), but moderately to −
3860A (
p
=
0.084). No influence of the number of cigarettes smoked per day by each subject was found. Heavy smokers (
n
=
48, with urinary nicotine plus its metabolites
≥0.69
mg/mmol creatinine) with variant allele −
2467delT or −
163A had significantly increased urinary mutagenicity (
p
<
0.01 and <0.05).
CYP1A2 genetic polymorphisms are shown to influence the CYP1A2 phenotype in smokers, −
2467 T
→
delT having the main effect
. This information is of interest for future studies assessing the possible role of tobacco smoke-inducible
CYP1A2 genotypes as individual susceptibility factors in exposure to carcinogens.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>16188490</pmid><doi>10.1016/j.mrgentox.2005.08.008</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1383-5718 |
| ispartof | Mutation research, 2005-11, Vol.587 (1), p.59-66 |
| issn | 1383-5718 0027-5107 1879-3592 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_20121744 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adolescent Adult Aged Biological and medical sciences Caffeine test CYP1A2 genotype CYP1A2 phenotype Cytochrome P-450 CYP1A2 - genetics Cytochrome P-450 CYP1A2 - metabolism Female Fundamental and applied biological sciences. Psychology Genetics of eukaryotes. Biological and molecular evolution Genotype Humans Individual susceptibility Male Medical sciences Middle Aged Phenotype Polymorphism, Genetic Promoter Regions, Genetic Salmonella typhimurium Smoking - adverse effects Smoking - genetics Tobacco smoke exposure Tobacco smoke-induced CYP1A2 activity Tobacco, tobacco smoking Toxicology Urinary mutagenicity |
| title | Influence of the genetic polymorphism in the 5′-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers |
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