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Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin
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| Zeitschriftentitel: | Circulation |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | Circulation, 118, 2008, suppl_18 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Ovid Technologies (Wolters Kluwer Health)
|
| Schlagwörter: |
| author_facet |
Mega, Jessica L Morrow, David A Brown, Alison Cannon, Christopher P Sabatine, Marc S Mega, Jessica L Morrow, David A Brown, Alison Cannon, Christopher P Sabatine, Marc S |
|---|---|
| author |
Mega, Jessica L Morrow, David A Brown, Alison Cannon, Christopher P Sabatine, Marc S |
| spellingShingle |
Mega, Jessica L Morrow, David A Brown, Alison Cannon, Christopher P Sabatine, Marc S Circulation Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin Physiology (medical) Cardiology and Cardiovascular Medicine |
| author_sort |
mega, jessica l |
| spelling |
Mega, Jessica L Morrow, David A Brown, Alison Cannon, Christopher P Sabatine, Marc S 0009-7322 1524-4539 Ovid Technologies (Wolters Kluwer Health) Physiology (medical) Cardiology and Cardiovascular Medicine http://dx.doi.org/10.1161/circ.118.suppl_18.s_649-a <jats:p> <jats:bold>Background</jats:bold> : LDL cholesterol (LDL-C) reduction in response to statins varies widely, with many patients not reaching target goals. We hypothesized that polymorphisms in LDL-C metabolism and statin pharmacokinetic genes would be associated with magnitude of LDL-C reduction with statin therapy. </jats:p> <jats:p> <jats:bold>Methods</jats:bold> : 49 tagging and candidate polymorphisms were selected in 9 genes and their associations with statin efficacy were tested in 1507 post-ACS subjects randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d. </jats:p> <jats:p> <jats:bold>Results</jats:bold> : Two variants in <jats:italic>APOE</jats:italic> (rs7412 and <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="gen" xlink:href="rs429358">rs429358</jats:ext-link> ) were significantly associated with baseline LDL-C (P=7.9×10 −9 and P=0.0032) and determine the isoforms ϵ2, ϵ3, and ϵ4 of apolipoprotein E. After adjustment for baseline LDL-C and clinical features, the percent reduction in LDL-C from baseline to day 30 was greatest in ϵ2 carriers, intermediate in ϵ3/ϵ3 individuals, and least in ϵ4 carriers with atorvastatin (P <jats:sub>trend</jats:sub> =0.00039) and pravastatin (P <jats:sub>trend</jats:sub> =0.00038), (Fig <jats:xref ref-type="fig" /> , Top). The percent of subjects achieving an LDL-C of ≤70 mg/dl was higher for ϵ2 carriers than ϵ4 carriers (atorvastatin P <jats:sub>trend</jats:sub> =0.00037 and pravastatin P <jats:sub>trend</jats:sub> =0.0084) (Fig <jats:xref ref-type="fig" /> , Bottom). The HR for CV death, MI, or stroke over 2 yrs for ϵ2 carriers vs ϵ3/ϵ3 individuals was 0.78 (95% CI 0.40 – 1.51). </jats:p> <jats:p> <jats:bold>Conclusion</jats:bold> : Evaluating genetic variants in 9 genes, we found that carriers of <jats:italic>APOE</jats:italic> ϵ2 versus ϵ4 had significantly lower baseline LDL-C, greater LDL-C reduction with atorvastatin or pravastatin, and more frequently achieved a goal of LDL-C ≤70 mg/dl. These findings add to the understanding of the genetic mechanisms that influence statin efficacy and suggest that common variants, such as the ones in <jats:italic>APOE</jats:italic> , may help tailor treatments. </jats:p> <jats:p> <jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" orientation="portrait" position="anchor" xlink:href="1135F1.jpeg" /> </jats:p> Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin Circulation |
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10.1161/circ.118.suppl_18.s_649-a |
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Ovid Technologies (Wolters Kluwer Health) |
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Circulation |
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| title |
Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_unstemmed |
Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_full |
Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_fullStr |
Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_full_unstemmed |
Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_short |
Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_sort |
abstract 1135: statin pharmacogenetics: identification of genetic variants that predict response to atorvastatin and pravastatin |
| topic |
Physiology (medical) Cardiology and Cardiovascular Medicine |
| url |
http://dx.doi.org/10.1161/circ.118.suppl_18.s_649-a |
| publishDate |
2008 |
| physical |
|
| description |
<jats:p>
<jats:bold>Background</jats:bold>
: LDL cholesterol (LDL-C) reduction in response to statins varies widely, with many patients not reaching target goals. We hypothesized that polymorphisms in LDL-C metabolism and statin pharmacokinetic genes would be associated with magnitude of LDL-C reduction with statin therapy.
</jats:p>
<jats:p>
<jats:bold>Methods</jats:bold>
: 49 tagging and candidate polymorphisms were selected in 9 genes and their associations with statin efficacy were tested in 1507 post-ACS subjects randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d.
</jats:p>
<jats:p>
<jats:bold>Results</jats:bold>
: Two variants in
<jats:italic>APOE</jats:italic>
(rs7412 and
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="gen" xlink:href="rs429358">rs429358</jats:ext-link>
) were significantly associated with baseline LDL-C (P=7.9×10 −9 and P=0.0032) and determine the isoforms ϵ2, ϵ3, and ϵ4 of apolipoprotein E. After adjustment for baseline LDL-C and clinical features, the percent reduction in LDL-C from baseline to day 30 was greatest in ϵ2 carriers, intermediate in ϵ3/ϵ3 individuals, and least in ϵ4 carriers with atorvastatin (P
<jats:sub>trend</jats:sub>
=0.00039) and pravastatin (P
<jats:sub>trend</jats:sub>
=0.00038), (Fig
<jats:xref ref-type="fig" />
, Top). The percent of subjects achieving an LDL-C of ≤70 mg/dl was higher for ϵ2 carriers than ϵ4 carriers (atorvastatin P
<jats:sub>trend</jats:sub>
=0.00037 and pravastatin P
<jats:sub>trend</jats:sub>
=0.0084) (Fig
<jats:xref ref-type="fig" />
, Bottom). The HR for CV death, MI, or stroke over 2 yrs for ϵ2 carriers vs ϵ3/ϵ3 individuals was 0.78 (95% CI 0.40 – 1.51).
</jats:p>
<jats:p>
<jats:bold>Conclusion</jats:bold>
: Evaluating genetic variants in 9 genes, we found that carriers of
<jats:italic>APOE</jats:italic>
ϵ2 versus ϵ4 had significantly lower baseline LDL-C, greater LDL-C reduction with atorvastatin or pravastatin, and more frequently achieved a goal of LDL-C ≤70 mg/dl. These findings add to the understanding of the genetic mechanisms that influence statin efficacy and suggest that common variants, such as the ones in
<jats:italic>APOE</jats:italic>
, may help tailor treatments.
</jats:p>
<jats:p>
<jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" orientation="portrait" position="anchor" xlink:href="1135F1.jpeg" />
</jats:p> |
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| author | Mega, Jessica L, Morrow, David A, Brown, Alison, Cannon, Christopher P, Sabatine, Marc S |
| author_facet | Mega, Jessica L, Morrow, David A, Brown, Alison, Cannon, Christopher P, Sabatine, Marc S, Mega, Jessica L, Morrow, David A, Brown, Alison, Cannon, Christopher P, Sabatine, Marc S |
| author_sort | mega, jessica l |
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| description | <jats:p> <jats:bold>Background</jats:bold> : LDL cholesterol (LDL-C) reduction in response to statins varies widely, with many patients not reaching target goals. We hypothesized that polymorphisms in LDL-C metabolism and statin pharmacokinetic genes would be associated with magnitude of LDL-C reduction with statin therapy. </jats:p> <jats:p> <jats:bold>Methods</jats:bold> : 49 tagging and candidate polymorphisms were selected in 9 genes and their associations with statin efficacy were tested in 1507 post-ACS subjects randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d. </jats:p> <jats:p> <jats:bold>Results</jats:bold> : Two variants in <jats:italic>APOE</jats:italic> (rs7412 and <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="gen" xlink:href="rs429358">rs429358</jats:ext-link> ) were significantly associated with baseline LDL-C (P=7.9×10 −9 and P=0.0032) and determine the isoforms ϵ2, ϵ3, and ϵ4 of apolipoprotein E. After adjustment for baseline LDL-C and clinical features, the percent reduction in LDL-C from baseline to day 30 was greatest in ϵ2 carriers, intermediate in ϵ3/ϵ3 individuals, and least in ϵ4 carriers with atorvastatin (P <jats:sub>trend</jats:sub> =0.00039) and pravastatin (P <jats:sub>trend</jats:sub> =0.00038), (Fig <jats:xref ref-type="fig" /> , Top). The percent of subjects achieving an LDL-C of ≤70 mg/dl was higher for ϵ2 carriers than ϵ4 carriers (atorvastatin P <jats:sub>trend</jats:sub> =0.00037 and pravastatin P <jats:sub>trend</jats:sub> =0.0084) (Fig <jats:xref ref-type="fig" /> , Bottom). The HR for CV death, MI, or stroke over 2 yrs for ϵ2 carriers vs ϵ3/ϵ3 individuals was 0.78 (95% CI 0.40 – 1.51). </jats:p> <jats:p> <jats:bold>Conclusion</jats:bold> : Evaluating genetic variants in 9 genes, we found that carriers of <jats:italic>APOE</jats:italic> ϵ2 versus ϵ4 had significantly lower baseline LDL-C, greater LDL-C reduction with atorvastatin or pravastatin, and more frequently achieved a goal of LDL-C ≤70 mg/dl. These findings add to the understanding of the genetic mechanisms that influence statin efficacy and suggest that common variants, such as the ones in <jats:italic>APOE</jats:italic> , may help tailor treatments. </jats:p> <jats:p> <jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" orientation="portrait" position="anchor" xlink:href="1135F1.jpeg" /> </jats:p> |
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| spelling | Mega, Jessica L Morrow, David A Brown, Alison Cannon, Christopher P Sabatine, Marc S 0009-7322 1524-4539 Ovid Technologies (Wolters Kluwer Health) Physiology (medical) Cardiology and Cardiovascular Medicine http://dx.doi.org/10.1161/circ.118.suppl_18.s_649-a <jats:p> <jats:bold>Background</jats:bold> : LDL cholesterol (LDL-C) reduction in response to statins varies widely, with many patients not reaching target goals. We hypothesized that polymorphisms in LDL-C metabolism and statin pharmacokinetic genes would be associated with magnitude of LDL-C reduction with statin therapy. </jats:p> <jats:p> <jats:bold>Methods</jats:bold> : 49 tagging and candidate polymorphisms were selected in 9 genes and their associations with statin efficacy were tested in 1507 post-ACS subjects randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d. </jats:p> <jats:p> <jats:bold>Results</jats:bold> : Two variants in <jats:italic>APOE</jats:italic> (rs7412 and <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="gen" xlink:href="rs429358">rs429358</jats:ext-link> ) were significantly associated with baseline LDL-C (P=7.9×10 −9 and P=0.0032) and determine the isoforms ϵ2, ϵ3, and ϵ4 of apolipoprotein E. After adjustment for baseline LDL-C and clinical features, the percent reduction in LDL-C from baseline to day 30 was greatest in ϵ2 carriers, intermediate in ϵ3/ϵ3 individuals, and least in ϵ4 carriers with atorvastatin (P <jats:sub>trend</jats:sub> =0.00039) and pravastatin (P <jats:sub>trend</jats:sub> =0.00038), (Fig <jats:xref ref-type="fig" /> , Top). The percent of subjects achieving an LDL-C of ≤70 mg/dl was higher for ϵ2 carriers than ϵ4 carriers (atorvastatin P <jats:sub>trend</jats:sub> =0.00037 and pravastatin P <jats:sub>trend</jats:sub> =0.0084) (Fig <jats:xref ref-type="fig" /> , Bottom). The HR for CV death, MI, or stroke over 2 yrs for ϵ2 carriers vs ϵ3/ϵ3 individuals was 0.78 (95% CI 0.40 – 1.51). </jats:p> <jats:p> <jats:bold>Conclusion</jats:bold> : Evaluating genetic variants in 9 genes, we found that carriers of <jats:italic>APOE</jats:italic> ϵ2 versus ϵ4 had significantly lower baseline LDL-C, greater LDL-C reduction with atorvastatin or pravastatin, and more frequently achieved a goal of LDL-C ≤70 mg/dl. These findings add to the understanding of the genetic mechanisms that influence statin efficacy and suggest that common variants, such as the ones in <jats:italic>APOE</jats:italic> , may help tailor treatments. </jats:p> <jats:p> <jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" orientation="portrait" position="anchor" xlink:href="1135F1.jpeg" /> </jats:p> Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin Circulation |
| spellingShingle | Mega, Jessica L, Morrow, David A, Brown, Alison, Cannon, Christopher P, Sabatine, Marc S, Circulation, Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin, Physiology (medical), Cardiology and Cardiovascular Medicine |
| title | Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_full | Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_fullStr | Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_full_unstemmed | Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_short | Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| title_sort | abstract 1135: statin pharmacogenetics: identification of genetic variants that predict response to atorvastatin and pravastatin |
| title_unstemmed | Abstract 1135: Statin Pharmacogenetics: Identification of Genetic Variants that Predict Response to Atorvastatin and Pravastatin |
| topic | Physiology (medical), Cardiology and Cardiovascular Medicine |
| url | http://dx.doi.org/10.1161/circ.118.suppl_18.s_649-a |