ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin treatment
This study investigated the effects of atorvastatin on ABCB1 and ABCC1 mRNA expression on peripheral blood mononuclear cells (PBMC) and their relationship with gene polymorphisms and lowering-cholesterol response. One hundred and thirty-six individuals with hypercholesterolemia were selected and tre...
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| Veröffentlicht in: | Biochemical pharmacology 2009, Vol.77 (1), p.66-75 |
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| creator | Rebecchi, Ivanise Marina Moretti Rodrigues, Alice Cristina Arazi, Simone Sorkin Genvigir, Fabiana Dalla Vecchia Willrich, Maria Alice Vieira Hirata, Mario Hiroyuki Soares, Sarah Aparecida Bertolami, Marcelo Chiara Faludi, André Arpad Bernik, Márcia Martins Silveira Dorea, Egidio Lima Dagli, Maria Lucia Zaidan Avanzo, José Luis Hirata, Rosario Dominguez Crespo |
| description | This study investigated the effects of atorvastatin on ABCB1 and ABCC1 mRNA expression on peripheral blood mononuclear cells (PBMC) and their relationship with gene polymorphisms and lowering-cholesterol response. One hundred and thirty-six individuals with hypercholesterolemia were selected and treated with atorvastatin (10
mg/day/4 weeks). Blood samples were collected for serum lipids and apolipoproteins measurements and DNA and RNA extraction. ABCB1 (C3435T and G2677T/A) and ABCC1 (G2012T) gene polymorphisms were identified by polymerase chain reaction-restriction (PCR)-RFLP and mRNA expression was measured in peripheral blood mononuclear cells by singleplex real-time PCR. ABCB1 polymorphisms were associated with risk for coronary artery disease (CAD) (
p
<
0.05). After atorvastatin treatment, both ABCB1 and ABCC1 genes showed 50% reduction of the mRNA expression (
p
<
0.05). Reduction of ABCB1 expression was associated with ABCB1 G2677T/A polymorphism (
p
=
0.039). Basal ABCB1 mRNA in the lower quartile (0.085: LDL-c
=
40.3
±
14.3%; apoB
=
32.5
±
10.7%;
p
<
0.05). ABCB1 substrates or inhibitors did not affect the baseline expression, while ABCB1 inhibitors reversed the effects of atorvastatin on both ABCB1 and ABCC1 transporters. In conclusion, ABCB1 and ABCC1 mRNA levels in PBMC are modulated by atorvastatin and ABCB1 G2677T/A polymorphism and ABCB1 baseline expression is related to differences in serum LDL cholesterol and apoB in response to atorvastatin. |
| doi_str_mv | 10.1016/j.bcp.2008.09.019 |
| format | Article |
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mg/day/4 weeks). Blood samples were collected for serum lipids and apolipoproteins measurements and DNA and RNA extraction. ABCB1 (C3435T and G2677T/A) and ABCC1 (G2012T) gene polymorphisms were identified by polymerase chain reaction-restriction (PCR)-RFLP and mRNA expression was measured in peripheral blood mononuclear cells by singleplex real-time PCR. ABCB1 polymorphisms were associated with risk for coronary artery disease (CAD) (
p
<
0.05). After atorvastatin treatment, both ABCB1 and ABCC1 genes showed 50% reduction of the mRNA expression (
p
<
0.05). Reduction of ABCB1 expression was associated with ABCB1 G2677T/A polymorphism (
p
=
0.039). Basal ABCB1 mRNA in the lower quartile (<0.024) was associated with lower reduction rate of serum low-density lipoprotein (LDL) cholesterol (33.4
±
12.4%) and apolipoprotein B (apoB) (17.0
±
31.3%) when compared with the higher quartile (>0.085: LDL-c
=
40.3
±
14.3%; apoB
=
32.5
±
10.7%;
p
<
0.05). ABCB1 substrates or inhibitors did not affect the baseline expression, while ABCB1 inhibitors reversed the effects of atorvastatin on both ABCB1 and ABCC1 transporters. In conclusion, ABCB1 and ABCC1 mRNA levels in PBMC are modulated by atorvastatin and ABCB1 G2677T/A polymorphism and ABCB1 baseline expression is related to differences in serum LDL cholesterol and apoB in response to atorvastatin.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/j.bcp.2008.09.019</identifier><identifier>PMID: 18851956</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>ABCB1 ; ABCC1 ; Aged ; Anticholesteremic Agents - pharmacology ; Atorvastatin ; Atorvastatin Calcium ; ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis ; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics ; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism ; Biological and medical sciences ; Female ; Gene expression ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - genetics ; Heptanoic Acids - pharmacology ; Humans ; Leukocytes, Mononuclear - drug effects ; Leukocytes, Mononuclear - metabolism ; Male ; Medical sciences ; Middle Aged ; Multidrug Resistance-Associated Proteins - biosynthesis ; Multidrug Resistance-Associated Proteins - genetics ; Multidrug Resistance-Associated Proteins - metabolism ; Pharmacogenetics ; Pharmacology. Drug treatments ; Polymorphism, Genetic - drug effects ; Polymorphism, Genetic - genetics ; Pyrroles - pharmacology ; Single nucleotide polymorphisms</subject><ispartof>Biochemical pharmacology, 2009, Vol.77 (1), p.66-75</ispartof><rights>2008 Elsevier Inc.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-d35da578a779e6121be1aae42fbfb75555206623f76a561a8f782bccaff7a9cc3</citedby><cites>FETCH-LOGICAL-c443t-d35da578a779e6121be1aae42fbfb75555206623f76a561a8f782bccaff7a9cc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006295208006461$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,4010,27900,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20955467$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18851956$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rebecchi, Ivanise Marina Moretti</creatorcontrib><creatorcontrib>Rodrigues, Alice Cristina</creatorcontrib><creatorcontrib>Arazi, Simone Sorkin</creatorcontrib><creatorcontrib>Genvigir, Fabiana Dalla Vecchia</creatorcontrib><creatorcontrib>Willrich, Maria Alice Vieira</creatorcontrib><creatorcontrib>Hirata, Mario Hiroyuki</creatorcontrib><creatorcontrib>Soares, Sarah Aparecida</creatorcontrib><creatorcontrib>Bertolami, Marcelo Chiara</creatorcontrib><creatorcontrib>Faludi, André Arpad</creatorcontrib><creatorcontrib>Bernik, Márcia Martins Silveira</creatorcontrib><creatorcontrib>Dorea, Egidio Lima</creatorcontrib><creatorcontrib>Dagli, Maria Lucia Zaidan</creatorcontrib><creatorcontrib>Avanzo, José Luis</creatorcontrib><creatorcontrib>Hirata, Rosario Dominguez Crespo</creatorcontrib><title>ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin treatment</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>This study investigated the effects of atorvastatin on ABCB1 and ABCC1 mRNA expression on peripheral blood mononuclear cells (PBMC) and their relationship with gene polymorphisms and lowering-cholesterol response. One hundred and thirty-six individuals with hypercholesterolemia were selected and treated with atorvastatin (10
mg/day/4 weeks). Blood samples were collected for serum lipids and apolipoproteins measurements and DNA and RNA extraction. ABCB1 (C3435T and G2677T/A) and ABCC1 (G2012T) gene polymorphisms were identified by polymerase chain reaction-restriction (PCR)-RFLP and mRNA expression was measured in peripheral blood mononuclear cells by singleplex real-time PCR. ABCB1 polymorphisms were associated with risk for coronary artery disease (CAD) (
p
<
0.05). After atorvastatin treatment, both ABCB1 and ABCC1 genes showed 50% reduction of the mRNA expression (
p
<
0.05). Reduction of ABCB1 expression was associated with ABCB1 G2677T/A polymorphism (
p
=
0.039). Basal ABCB1 mRNA in the lower quartile (<0.024) was associated with lower reduction rate of serum low-density lipoprotein (LDL) cholesterol (33.4
±
12.4%) and apolipoprotein B (apoB) (17.0
±
31.3%) when compared with the higher quartile (>0.085: LDL-c
=
40.3
±
14.3%; apoB
=
32.5
±
10.7%;
p
<
0.05). ABCB1 substrates or inhibitors did not affect the baseline expression, while ABCB1 inhibitors reversed the effects of atorvastatin on both ABCB1 and ABCC1 transporters. In conclusion, ABCB1 and ABCC1 mRNA levels in PBMC are modulated by atorvastatin and ABCB1 G2677T/A polymorphism and ABCB1 baseline expression is related to differences in serum LDL cholesterol and apoB in response to atorvastatin.</description><subject>ABCB1</subject><subject>ABCC1</subject><subject>Aged</subject><subject>Anticholesteremic Agents - pharmacology</subject><subject>Atorvastatin</subject><subject>Atorvastatin Calcium</subject><subject>ATP Binding Cassette Transporter, Sub-Family B</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - genetics</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</subject><subject>Biological and medical sciences</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation - genetics</subject><subject>Heptanoic Acids - pharmacology</subject><subject>Humans</subject><subject>Leukocytes, Mononuclear - drug effects</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multidrug Resistance-Associated Proteins - biosynthesis</subject><subject>Multidrug Resistance-Associated Proteins - genetics</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>Pharmacogenetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Genetic - drug effects</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Pyrroles - pharmacology</subject><subject>Single nucleotide polymorphisms</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhiMEokvhB3BBvsBtg-3EX-LUrqAgVeICZ2vijKlXiRPsbMX-e5zuCm6tZclj6ZlX9jxV9ZbRmlEmP-7rzs01p1TX1NSUmWfVhmnVbLmR-nm1oZTKUgt-Ub3Keb9etWQvqwumtWBGyE11vLreXTMCsSel2jGCf-aEOYcpkhDJjCnMd5hgIOMUp3hwA0IiDochk1B29MMBo8OedEfyCyOSeRqO45Tmu5DH_BAMy5TuIS-wlMQlISwjxuV19cLDkPHN-bysfn75_GP3dXv7_ebb7up269q2WbZ9I3oQSoNSBiXjrEMGgC33ne-UKItTKXnjlQQhGWivNO-cA-8VGOeay-rDKXdO0-8D5sWOIa8fgIjTIVspFdeUtk-CZc7CmFY_CTKjacPlCrIT6NKUc0Jv5xRGSEfLqF0N2r0tBtdkbamxxWDpeXcOP3Qj9v87zsoK8P4MQHYw-ATRhfyP49QI0UpVuE8nDstw7wMmm114UBUSusX2U3jkGX8BSLC6Dw</recordid><startdate>2009</startdate><enddate>2009</enddate><creator>Rebecchi, Ivanise Marina Moretti</creator><creator>Rodrigues, Alice Cristina</creator><creator>Arazi, Simone Sorkin</creator><creator>Genvigir, Fabiana Dalla Vecchia</creator><creator>Willrich, Maria Alice Vieira</creator><creator>Hirata, Mario Hiroyuki</creator><creator>Soares, Sarah Aparecida</creator><creator>Bertolami, Marcelo Chiara</creator><creator>Faludi, André Arpad</creator><creator>Bernik, Márcia Martins Silveira</creator><creator>Dorea, Egidio Lima</creator><creator>Dagli, Maria Lucia Zaidan</creator><creator>Avanzo, José Luis</creator><creator>Hirata, Rosario Dominguez Crespo</creator><general>Elsevier Inc</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>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>2009</creationdate><title>ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin treatment</title><author>Rebecchi, Ivanise Marina Moretti ; Rodrigues, Alice Cristina ; Arazi, Simone Sorkin ; Genvigir, Fabiana Dalla Vecchia ; Willrich, Maria Alice Vieira ; Hirata, Mario Hiroyuki ; Soares, Sarah Aparecida ; Bertolami, Marcelo Chiara ; Faludi, André Arpad ; Bernik, Márcia Martins Silveira ; Dorea, Egidio Lima ; Dagli, Maria Lucia Zaidan ; Avanzo, José Luis ; Hirata, Rosario Dominguez Crespo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-d35da578a779e6121be1aae42fbfb75555206623f76a561a8f782bccaff7a9cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>ABCB1</topic><topic>ABCC1</topic><topic>Aged</topic><topic>Anticholesteremic Agents - pharmacology</topic><topic>Atorvastatin</topic><topic>Atorvastatin Calcium</topic><topic>ATP Binding Cassette Transporter, Sub-Family B</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - genetics</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</topic><topic>Biological and medical sciences</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Expression Regulation - genetics</topic><topic>Heptanoic Acids - pharmacology</topic><topic>Humans</topic><topic>Leukocytes, Mononuclear - drug effects</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multidrug Resistance-Associated Proteins - biosynthesis</topic><topic>Multidrug Resistance-Associated Proteins - genetics</topic><topic>Multidrug Resistance-Associated Proteins - metabolism</topic><topic>Pharmacogenetics</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Genetic - drug effects</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Pyrroles - pharmacology</topic><topic>Single nucleotide polymorphisms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rebecchi, Ivanise Marina Moretti</creatorcontrib><creatorcontrib>Rodrigues, Alice Cristina</creatorcontrib><creatorcontrib>Arazi, Simone Sorkin</creatorcontrib><creatorcontrib>Genvigir, Fabiana Dalla Vecchia</creatorcontrib><creatorcontrib>Willrich, Maria Alice Vieira</creatorcontrib><creatorcontrib>Hirata, Mario Hiroyuki</creatorcontrib><creatorcontrib>Soares, Sarah Aparecida</creatorcontrib><creatorcontrib>Bertolami, Marcelo Chiara</creatorcontrib><creatorcontrib>Faludi, André Arpad</creatorcontrib><creatorcontrib>Bernik, Márcia Martins Silveira</creatorcontrib><creatorcontrib>Dorea, Egidio Lima</creatorcontrib><creatorcontrib>Dagli, Maria Lucia Zaidan</creatorcontrib><creatorcontrib>Avanzo, José Luis</creatorcontrib><creatorcontrib>Hirata, Rosario Dominguez Crespo</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>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rebecchi, Ivanise Marina Moretti</au><au>Rodrigues, Alice Cristina</au><au>Arazi, Simone Sorkin</au><au>Genvigir, Fabiana Dalla Vecchia</au><au>Willrich, Maria Alice Vieira</au><au>Hirata, Mario Hiroyuki</au><au>Soares, Sarah Aparecida</au><au>Bertolami, Marcelo Chiara</au><au>Faludi, André Arpad</au><au>Bernik, Márcia Martins Silveira</au><au>Dorea, Egidio Lima</au><au>Dagli, Maria Lucia Zaidan</au><au>Avanzo, José Luis</au><au>Hirata, Rosario Dominguez Crespo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin treatment</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>2009</date><risdate>2009</risdate><volume>77</volume><issue>1</issue><spage>66</spage><epage>75</epage><pages>66-75</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><abstract>This study investigated the effects of atorvastatin on ABCB1 and ABCC1 mRNA expression on peripheral blood mononuclear cells (PBMC) and their relationship with gene polymorphisms and lowering-cholesterol response. One hundred and thirty-six individuals with hypercholesterolemia were selected and treated with atorvastatin (10
mg/day/4 weeks). Blood samples were collected for serum lipids and apolipoproteins measurements and DNA and RNA extraction. ABCB1 (C3435T and G2677T/A) and ABCC1 (G2012T) gene polymorphisms were identified by polymerase chain reaction-restriction (PCR)-RFLP and mRNA expression was measured in peripheral blood mononuclear cells by singleplex real-time PCR. ABCB1 polymorphisms were associated with risk for coronary artery disease (CAD) (
p
<
0.05). After atorvastatin treatment, both ABCB1 and ABCC1 genes showed 50% reduction of the mRNA expression (
p
<
0.05). Reduction of ABCB1 expression was associated with ABCB1 G2677T/A polymorphism (
p
=
0.039). Basal ABCB1 mRNA in the lower quartile (<0.024) was associated with lower reduction rate of serum low-density lipoprotein (LDL) cholesterol (33.4
±
12.4%) and apolipoprotein B (apoB) (17.0
±
31.3%) when compared with the higher quartile (>0.085: LDL-c
=
40.3
±
14.3%; apoB
=
32.5
±
10.7%;
p
<
0.05). ABCB1 substrates or inhibitors did not affect the baseline expression, while ABCB1 inhibitors reversed the effects of atorvastatin on both ABCB1 and ABCC1 transporters. In conclusion, ABCB1 and ABCC1 mRNA levels in PBMC are modulated by atorvastatin and ABCB1 G2677T/A polymorphism and ABCB1 baseline expression is related to differences in serum LDL cholesterol and apoB in response to atorvastatin.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>18851956</pmid><doi>10.1016/j.bcp.2008.09.019</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Biochemical pharmacology, 2009, Vol.77 (1), p.66-75 |
| issn | 0006-2952 1873-2968 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_66728004 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | ABCB1 ABCC1 Aged Anticholesteremic Agents - pharmacology Atorvastatin Atorvastatin Calcium ATP Binding Cassette Transporter, Sub-Family B ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis ATP-Binding Cassette, Sub-Family B, Member 1 - genetics ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Biological and medical sciences Female Gene expression Gene Expression Regulation - drug effects Gene Expression Regulation - genetics Heptanoic Acids - pharmacology Humans Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - metabolism Male Medical sciences Middle Aged Multidrug Resistance-Associated Proteins - biosynthesis Multidrug Resistance-Associated Proteins - genetics Multidrug Resistance-Associated Proteins - metabolism Pharmacogenetics Pharmacology. Drug treatments Polymorphism, Genetic - drug effects Polymorphism, Genetic - genetics Pyrroles - pharmacology Single nucleotide polymorphisms |
| title | ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin treatment |
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