Differences in CYP2C9 Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex
Global personalized medicine demands the characterization of person-to-person and between-population differences in drug pharmacokinetics and pharmacodynamics. CYP2C9 pharmacokinetic pathway is subject to modulation by both genetic and environmental factors. CYP2C9 genotype-based dose recommendation...
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| Veröffentlicht in: | Omics (Larchmont, N.Y.) N.Y.), 2015-06, Vol.19 (6), p.346-353 |
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| creator | Hatta, Fazleen H.M. Lundblad, Mia Ramsjo, Margareta Kang, Ju-Hee Roh, Hyung-Keun Bertilsson, Leif Eliasson, Erik Aklillu, Eleni |
| description | Global personalized medicine demands the characterization of person-to-person and between-population differences in drug pharmacokinetics and pharmacodynamics. CYP2C9 pharmacokinetic pathway is subject to modulation by both genetic and environmental factors.
CYP2C9
genotype-based dose recommendations (e.g., for warfarin) is advocated. However, the overall contribution of genotype for variation in enzyme activity may differ between populations. We evaluated the importance of ethnicity, genotype, smoking, body weight, age, and sex for CYP2C9 enzyme activity.
CYP2C9
genotype and phenotype was determined in 148 Swedes and 146 Koreans using losartan as a probe. CYP2C9 enzyme activity was assed using urinary losartan/metabolite E-3174 ratio. The frequency of
CYP2C9
defective variant alleles (*
2
and *3) was significantly higher in Swedes (10.8% and 12.5%) than in Koreans (0% and 5.8%). In matched genotypes, CYP2C9 enzyme activity was significantly lower in Swedes compared to Koreans (
p |
| doi_str_mv | 10.1089/omi.2015.0022 |
| format | Article |
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CYP2C9
genotype-based dose recommendations (e.g., for warfarin) is advocated. However, the overall contribution of genotype for variation in enzyme activity may differ between populations. We evaluated the importance of ethnicity, genotype, smoking, body weight, age, and sex for CYP2C9 enzyme activity.
CYP2C9
genotype and phenotype was determined in 148 Swedes and 146 Koreans using losartan as a probe. CYP2C9 enzyme activity was assed using urinary losartan/metabolite E-3174 ratio. The frequency of
CYP2C9
defective variant alleles (*
2
and *3) was significantly higher in Swedes (10.8% and 12.5%) than in Koreans (0% and 5.8%). In matched genotypes, CYP2C9 enzyme activity was significantly lower in Swedes compared to Koreans (
p
<0.0001). In a univariate analysis, age, weight, ethnicity, genotype, and smoking were significant predictors of CYP2C9 phenotype. A stepwise multivariate analysis indicated ethnicity, genotype, and smoking remained as significant predictors of CYP2C9 enzyme activity, accounting for 50% of the total variance. In both study populations,
CYP2C9
genotype was a significant predictor of CYP2C9 enzyme activity, but its contribution in explaining the total variance was lower in Koreans (26.6%) than Swedes (40%). In conclusion, we report significantly lower CYP2C9 enzyme activity in Swedes compared to Koreans, partly but not exclusively due to
CYP2C9
pharmacogenetic variations. Ethnicity and environment factors need to be considered together with genotype for population-specific dose optimization and global personalized medicine.</description><identifier>ISSN: 1536-2310</identifier><identifier>ISSN: 1557-8100</identifier><identifier>EISSN: 1557-8100</identifier><identifier>DOI: 10.1089/omi.2015.0022</identifier><identifier>PMID: 25977991</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Adult ; Cytochrome P-450 CYP2C9 - genetics ; Cytochrome P-450 CYP2C9 - metabolism ; Cytochrome P-450 CYP3A - metabolism ; Female ; Gene Frequency - genetics ; Genotype ; Humans ; Korea ; Male ; Multivariate Analysis ; Original Articles ; Pharmacogenetics ; Pharmacokinetics ; Phenotype ; Precision Medicine - methods ; Smoking ; Young Adult</subject><ispartof>Omics (Larchmont, N.Y.), 2015-06, Vol.19 (6), p.346-353</ispartof><rights>2015, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-2c461e6b94206e0bc5b1115ef0845e04694bd7948b9248fcb662a1d0532671c33</citedby><cites>FETCH-LOGICAL-c411t-2c461e6b94206e0bc5b1115ef0845e04694bd7948b9248fcb662a1d0532671c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25977991$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:shh:diva-2119$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:132313238$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Hatta, Fazleen H.M.</creatorcontrib><creatorcontrib>Lundblad, Mia</creatorcontrib><creatorcontrib>Ramsjo, Margareta</creatorcontrib><creatorcontrib>Kang, Ju-Hee</creatorcontrib><creatorcontrib>Roh, Hyung-Keun</creatorcontrib><creatorcontrib>Bertilsson, Leif</creatorcontrib><creatorcontrib>Eliasson, Erik</creatorcontrib><creatorcontrib>Aklillu, Eleni</creatorcontrib><title>Differences in CYP2C9 Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex</title><title>Omics (Larchmont, N.Y.)</title><addtitle>OMICS</addtitle><description>Global personalized medicine demands the characterization of person-to-person and between-population differences in drug pharmacokinetics and pharmacodynamics. CYP2C9 pharmacokinetic pathway is subject to modulation by both genetic and environmental factors.
CYP2C9
genotype-based dose recommendations (e.g., for warfarin) is advocated. However, the overall contribution of genotype for variation in enzyme activity may differ between populations. We evaluated the importance of ethnicity, genotype, smoking, body weight, age, and sex for CYP2C9 enzyme activity.
CYP2C9
genotype and phenotype was determined in 148 Swedes and 146 Koreans using losartan as a probe. CYP2C9 enzyme activity was assed using urinary losartan/metabolite E-3174 ratio. The frequency of
CYP2C9
defective variant alleles (*
2
and *3) was significantly higher in Swedes (10.8% and 12.5%) than in Koreans (0% and 5.8%). In matched genotypes, CYP2C9 enzyme activity was significantly lower in Swedes compared to Koreans (
p
<0.0001). In a univariate analysis, age, weight, ethnicity, genotype, and smoking were significant predictors of CYP2C9 phenotype. A stepwise multivariate analysis indicated ethnicity, genotype, and smoking remained as significant predictors of CYP2C9 enzyme activity, accounting for 50% of the total variance. In both study populations,
CYP2C9
genotype was a significant predictor of CYP2C9 enzyme activity, but its contribution in explaining the total variance was lower in Koreans (26.6%) than Swedes (40%). In conclusion, we report significantly lower CYP2C9 enzyme activity in Swedes compared to Koreans, partly but not exclusively due to
CYP2C9
pharmacogenetic variations. Ethnicity and environment factors need to be considered together with genotype for population-specific dose optimization and global personalized medicine.</description><subject>Adult</subject><subject>Cytochrome P-450 CYP2C9 - genetics</subject><subject>Cytochrome P-450 CYP2C9 - metabolism</subject><subject>Cytochrome P-450 CYP3A - metabolism</subject><subject>Female</subject><subject>Gene Frequency - genetics</subject><subject>Genotype</subject><subject>Humans</subject><subject>Korea</subject><subject>Male</subject><subject>Multivariate Analysis</subject><subject>Original Articles</subject><subject>Pharmacogenetics</subject><subject>Pharmacokinetics</subject><subject>Phenotype</subject><subject>Precision Medicine - methods</subject><subject>Smoking</subject><subject>Young Adult</subject><issn>1536-2310</issn><issn>1557-8100</issn><issn>1557-8100</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1v0zAUhiMEYmNwyS3yJRJN8XGcD3PXdWUghphWQOLKcpKT1iyxi52uZL-In4mjlnKFuPLxq8fPsfRG0XOgU6CFeG07PWUU0imljD2ITiFN87gASh-Oc5LFLAF6Ej3x_nsgIGPJ4-iEpSLPhYDT6NeFbhp0aCr0RBsy_3bN5oJcorH9sEGiTE0W5n7okMyqXt_pfiDn2O8QDVnusA6vRuSDdaiMJ7YhN9jinQo-0lhHrtF5a1Sr77EmH7HWlTb4htzYFkd40a9NiPphclw5IcvO3mqzmpDZKtxG_RJ_Po0eNar1-OxwnkVf3i4-z9_FV58u389nV3HFAfqYVTwDzErBGc2QllVaAkCKDS14ipRngpd1LnhRCsaLpiqzjCmoaZqwLIcqSc6ieO_1O9xsS7lxulNukFZpeYhuw4QyhYQXaeBf_ZO_0F9n0rqV9Ou1ZAAi0C_39MbZH1v0vey0r7BtlUG79RJyKGieccb_fqRy1nuHzVENVI7Vy1C9HKuXY_WBf3FQb8sO6yP9p-sAJHtgjJUxrcYSXf8f7W_Qubt6</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Hatta, Fazleen H.M.</creator><creator>Lundblad, Mia</creator><creator>Ramsjo, Margareta</creator><creator>Kang, Ju-Hee</creator><creator>Roh, Hyung-Keun</creator><creator>Bertilsson, Leif</creator><creator>Eliasson, Erik</creator><creator>Aklillu, Eleni</creator><general>Mary Ann Liebert, Inc</general><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>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DF4</scope></search><sort><creationdate>20150601</creationdate><title>Differences in CYP2C9 Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex</title><author>Hatta, Fazleen H.M. ; Lundblad, Mia ; Ramsjo, Margareta ; Kang, Ju-Hee ; Roh, Hyung-Keun ; Bertilsson, Leif ; Eliasson, Erik ; Aklillu, Eleni</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-2c461e6b94206e0bc5b1115ef0845e04694bd7948b9248fcb662a1d0532671c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Cytochrome P-450 CYP2C9 - genetics</topic><topic>Cytochrome P-450 CYP2C9 - metabolism</topic><topic>Cytochrome P-450 CYP3A - metabolism</topic><topic>Female</topic><topic>Gene Frequency - genetics</topic><topic>Genotype</topic><topic>Humans</topic><topic>Korea</topic><topic>Male</topic><topic>Multivariate Analysis</topic><topic>Original Articles</topic><topic>Pharmacogenetics</topic><topic>Pharmacokinetics</topic><topic>Phenotype</topic><topic>Precision Medicine - methods</topic><topic>Smoking</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hatta, Fazleen H.M.</creatorcontrib><creatorcontrib>Lundblad, Mia</creatorcontrib><creatorcontrib>Ramsjo, Margareta</creatorcontrib><creatorcontrib>Kang, Ju-Hee</creatorcontrib><creatorcontrib>Roh, Hyung-Keun</creatorcontrib><creatorcontrib>Bertilsson, Leif</creatorcontrib><creatorcontrib>Eliasson, Erik</creatorcontrib><creatorcontrib>Aklillu, Eleni</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Sophiahemmet Högskola</collection><jtitle>Omics (Larchmont, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hatta, Fazleen H.M.</au><au>Lundblad, Mia</au><au>Ramsjo, Margareta</au><au>Kang, Ju-Hee</au><au>Roh, Hyung-Keun</au><au>Bertilsson, Leif</au><au>Eliasson, Erik</au><au>Aklillu, Eleni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differences in CYP2C9 Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex</atitle><jtitle>Omics (Larchmont, N.Y.)</jtitle><addtitle>OMICS</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>19</volume><issue>6</issue><spage>346</spage><epage>353</epage><pages>346-353</pages><issn>1536-2310</issn><issn>1557-8100</issn><eissn>1557-8100</eissn><abstract>Global personalized medicine demands the characterization of person-to-person and between-population differences in drug pharmacokinetics and pharmacodynamics. CYP2C9 pharmacokinetic pathway is subject to modulation by both genetic and environmental factors.
CYP2C9
genotype-based dose recommendations (e.g., for warfarin) is advocated. However, the overall contribution of genotype for variation in enzyme activity may differ between populations. We evaluated the importance of ethnicity, genotype, smoking, body weight, age, and sex for CYP2C9 enzyme activity.
CYP2C9
genotype and phenotype was determined in 148 Swedes and 146 Koreans using losartan as a probe. CYP2C9 enzyme activity was assed using urinary losartan/metabolite E-3174 ratio. The frequency of
CYP2C9
defective variant alleles (*
2
and *3) was significantly higher in Swedes (10.8% and 12.5%) than in Koreans (0% and 5.8%). In matched genotypes, CYP2C9 enzyme activity was significantly lower in Swedes compared to Koreans (
p
<0.0001). In a univariate analysis, age, weight, ethnicity, genotype, and smoking were significant predictors of CYP2C9 phenotype. A stepwise multivariate analysis indicated ethnicity, genotype, and smoking remained as significant predictors of CYP2C9 enzyme activity, accounting for 50% of the total variance. In both study populations,
CYP2C9
genotype was a significant predictor of CYP2C9 enzyme activity, but its contribution in explaining the total variance was lower in Koreans (26.6%) than Swedes (40%). In conclusion, we report significantly lower CYP2C9 enzyme activity in Swedes compared to Koreans, partly but not exclusively due to
CYP2C9
pharmacogenetic variations. Ethnicity and environment factors need to be considered together with genotype for population-specific dose optimization and global personalized medicine.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>25977991</pmid><doi>10.1089/omi.2015.0022</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1536-2310 |
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| issn | 1536-2310 1557-8100 1557-8100 |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Adult Cytochrome P-450 CYP2C9 - genetics Cytochrome P-450 CYP2C9 - metabolism Cytochrome P-450 CYP3A - metabolism Female Gene Frequency - genetics Genotype Humans Korea Male Multivariate Analysis Original Articles Pharmacogenetics Pharmacokinetics Phenotype Precision Medicine - methods Smoking Young Adult |
| title | Differences in CYP2C9 Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex |
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