Genetic determinants of statin intolerance
<p>Abstract</p> <p>Background</p> <p>Statin-related skeletal muscle disorders range from benign myalgias – such as non-specific muscle aches or joint pains without elevated serum creatinine kinase (CK) concentration – to true myositis with >10-fold elevation of serum...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2007-03-01
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| Series: | Lipids in Health and Disease |
| Online Access: | http://www.lipidworld.com/content/6/1/7 |
| _version_ | 1811249879941382144 |
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| author | Pollex Rebecca L Miskie Brooke A Ban Matthew R Oh Jisun Hegele Robert A |
| author_facet | Pollex Rebecca L Miskie Brooke A Ban Matthew R Oh Jisun Hegele Robert A |
| author_sort | Pollex Rebecca L |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Statin-related skeletal muscle disorders range from benign myalgias – such as non-specific muscle aches or joint pains without elevated serum creatinine kinase (CK) concentration – to true myositis with >10-fold elevation of serum CK, to rhabdomyolysis and myoglobinuria. The genetic basis of statin-related muscle disorders is largely unknown. Because mutations in the <it>COQ2 </it>gene are associated with severe inherited myopathy, we hypothesized that common, mild genetic variation in <it>COQ2 </it>would be associated with inter-individual variation in statin intolerance. We studied 133 subjects who developed myopathy on statin monotherapy and 158 matched controls who tolerated statins without incident or complaint.</p> <p>Results</p> <p><it>COQ2 </it>genotypes, based on two single nucleotide polymorphisms (SNP1 and SNP2) and a 2-SNP haplotype, all showed significant associations with statin intolerance. Specifically, the odds ratios (with 95% confidence intervals) for increased risk of statin intolerance among homozygotes for the rare alleles were 2.42 (0.99 to 5.89), 2.33 (1.13 to 4.81) and 2.58 (1.26 to 5.28) for SNP1 and SNP2 genotypes, and the 2-SNP haplotype, respectively.</p> <p>Conclusion</p> <p>These preliminary pharmacogenetic results, if confirmed, are consistent with the idea that statin intolerance which is manifested primarily through muscle symptoms is associated with genomic variation in <it>COQ2 </it>and thus perhaps with the CoQ10 pathway.</p> |
| first_indexed | 2024-04-12T15:55:13Z |
| format | Article |
| id | doaj.art-8e1c84193c074475935441e7fe0f5149 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-04-12T15:55:13Z |
| publishDate | 2007-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-8e1c84193c074475935441e7fe0f51492022-12-22T03:26:23ZengBMCLipids in Health and Disease1476-511X2007-03-0161710.1186/1476-511X-6-7Genetic determinants of statin intolerancePollex Rebecca LMiskie Brooke ABan Matthew ROh JisunHegele Robert A<p>Abstract</p> <p>Background</p> <p>Statin-related skeletal muscle disorders range from benign myalgias – such as non-specific muscle aches or joint pains without elevated serum creatinine kinase (CK) concentration – to true myositis with >10-fold elevation of serum CK, to rhabdomyolysis and myoglobinuria. The genetic basis of statin-related muscle disorders is largely unknown. Because mutations in the <it>COQ2 </it>gene are associated with severe inherited myopathy, we hypothesized that common, mild genetic variation in <it>COQ2 </it>would be associated with inter-individual variation in statin intolerance. We studied 133 subjects who developed myopathy on statin monotherapy and 158 matched controls who tolerated statins without incident or complaint.</p> <p>Results</p> <p><it>COQ2 </it>genotypes, based on two single nucleotide polymorphisms (SNP1 and SNP2) and a 2-SNP haplotype, all showed significant associations with statin intolerance. Specifically, the odds ratios (with 95% confidence intervals) for increased risk of statin intolerance among homozygotes for the rare alleles were 2.42 (0.99 to 5.89), 2.33 (1.13 to 4.81) and 2.58 (1.26 to 5.28) for SNP1 and SNP2 genotypes, and the 2-SNP haplotype, respectively.</p> <p>Conclusion</p> <p>These preliminary pharmacogenetic results, if confirmed, are consistent with the idea that statin intolerance which is manifested primarily through muscle symptoms is associated with genomic variation in <it>COQ2 </it>and thus perhaps with the CoQ10 pathway.</p>http://www.lipidworld.com/content/6/1/7 |
| spellingShingle | Pollex Rebecca L Miskie Brooke A Ban Matthew R Oh Jisun Hegele Robert A Genetic determinants of statin intolerance Lipids in Health and Disease |
| title | Genetic determinants of statin intolerance |
| title_full | Genetic determinants of statin intolerance |
| title_fullStr | Genetic determinants of statin intolerance |
| title_full_unstemmed | Genetic determinants of statin intolerance |
| title_short | Genetic determinants of statin intolerance |
| title_sort | genetic determinants of statin intolerance |
| url | http://www.lipidworld.com/content/6/1/7 |
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