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Are you a fast metabolizer of medicines?
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<blockquote data-quote="Nelson Vergel" data-source="post: 37701" data-attributes="member: 3"><p><strong>The CYP3A418 Genotype in the Cytochrome P450 3A4 Gene, a Rapid Metabolizer of Sex Steroids, Is Associated With Low Bone Mineral Density</strong></p><p></p><p>by Kang, YS; Park, SY; Yim, CH; Kwak, HS; Gajendrarao, P; Krishnamoorthy, N; Yun, S&#8208;C; Lee, KW; Han, KO</p><p></p><p>Osteoporosis is influenced by genetic factors. The interindividual variability in the activity of CYP3A, the metabolic enzyme of sex hormones, may result from genetic polymorphisms. In a study of 2,178 women of ages 40 to79 years, the presence of the CYP3A4*18 variant was found to be significantly associated with low bone mass. In vitro functional analyses indicate that CYP3A4*18 is a gain of estrogens and testosterone; in vivo pharmacokinetics using midazolam (MDZ) verify the altered activity of the CYP3A4*18, showing lower metabolic turnover in the mutant than in the wild type. Molecular modeling reveals the structural changes in the substrate recognition sites of CYP3A4*18 that can cause changes in enzymatic activity and that potentially account for the difference between the catalytic activities of estrogen and MDZ, depending on the genotype. The results indicate that a genetic variation in the CYP3A4 gene—as a gain function mutation in the metabolism of certain CYP3A substrates, including sex steroids—may predispose individuals to osteoporosis.</p><p></p><p>Clinical Pharmacology & Therapeutics (2009); 85 , 3, 312-318 doi: 10.1038/clpt.2008.215</p></blockquote><p></p>
[QUOTE="Nelson Vergel, post: 37701, member: 3"] [B]The CYP3A418 Genotype in the Cytochrome P450 3A4 Gene, a Rapid Metabolizer of Sex Steroids, Is Associated With Low Bone Mineral Density[/B] by Kang, YS; Park, SY; Yim, CH; Kwak, HS; Gajendrarao, P; Krishnamoorthy, N; Yun, S‐C; Lee, KW; Han, KO Osteoporosis is influenced by genetic factors. The interindividual variability in the activity of CYP3A, the metabolic enzyme of sex hormones, may result from genetic polymorphisms. In a study of 2,178 women of ages 40 to79 years, the presence of the CYP3A4*18 variant was found to be significantly associated with low bone mass. In vitro functional analyses indicate that CYP3A4*18 is a gain of estrogens and testosterone; in vivo pharmacokinetics using midazolam (MDZ) verify the altered activity of the CYP3A4*18, showing lower metabolic turnover in the mutant than in the wild type. Molecular modeling reveals the structural changes in the substrate recognition sites of CYP3A4*18 that can cause changes in enzymatic activity and that potentially account for the difference between the catalytic activities of estrogen and MDZ, depending on the genotype. The results indicate that a genetic variation in the CYP3A4 gene—as a gain function mutation in the metabolism of certain CYP3A substrates, including sex steroids—may predispose individuals to osteoporosis. Clinical Pharmacology & Therapeutics (2009); 85 , 3, 312-318 doi: 10.1038/clpt.2008.215 [/QUOTE]
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