| Genetic polymorphisms of L-type calcium channel alpha1C and alpha1D subunit genes are associated with sensitivity to the antihypertensive effects of L-type dihydropyridine calcium-channel blockers. | |
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MedLine Citation:
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PMID: 19225208 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The response of blood pressure (BP) to L-type dihydropyridine calcium-channel blockers (dCCBs) differs among individuals. METHODS AND RESULTS: A pharmacogenomic analysis was undertaken in 161 patients with essential hypertension who were treated with dCCBs to study whether genetic polymorphisms of the calcium channel alpha1C and alpha1D subunit genes, CACNA1C and CACNA1D, are associated with the antihypertensive effects of dCCBs. Responders were defined as those in whom systolic BP (SBP) was lowered by more than 20 mmHg or diastolic BP (DBP) was lowered by more than 10 mmHg after treatment with dCCBs. Eleven sequence-proven polymorphisms of CACNA1C and 5 common polymorphisms of CACNA1D chosen from a public database were subjected to genotypic analysis. The comparison of polymorphism prevalence between responders and nonresponders showed significant differences in CACNA1D rs312481G>A and rs3774426C>T, and in CACNA1C 527974G>A. There were significant differences in SBP or DBP between alleles in these single nucleotide polymorphisms (SNPs). A much more significant reduction in BP was observed for the combined presence of these SNPs. CONCLUSIONS: Three SNPs in CACNA1D or CACNA1C are genetic polymorphisms conferring sensitivity to the antihypertensive effects of L-type dCCBs in patients with hypertension. The BP reduction by L-type dCCBs might be predicted by evaluating these polymorphisms. |
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Authors:
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Kei Kamide; Jin Yang; Tetsutaro Matayoshi; Shin Takiuchi; Takeshi Horio; Masayoshi Yoshii; Yoshikazu Miwa; Hisayo Yasuda; Fumiki Yoshihara; Satoko Nakamura; Hajime Nakahama; Toshiyuki Miyata; Yuhei Kawano |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-02-17 |
Journal Detail:
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Title: Circulation journal : official journal of the Japanese Circulation Society Volume: 73 ISSN: 1346-9843 ISO Abbreviation: Circ. J. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-25 Completed Date: 2009-06-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101137683 Medline TA: Circ J Country: Japan |
Other Details:
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Languages: eng Pagination: 732-40 Citation Subset: IM |
Affiliation:
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Division of Hypertension and Nephrology, Research Institute, National Cardiovascular Center, Suita, Japan. kamide@hsp.ncvc.go.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Alleles Calcium Channel Blockers / administration & dosage* Calcium Channels, L-Type / genetics* Dihydropyridines / administration & dosage* Female Humans Hypertension / drug therapy*, genetics*, physiopathology Male Middle Aged Polymorphism, Single Nucleotide* |
| Chemical | |
Reg. No./Substance:
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0/CACNA1C protein, human; 0/CACNA1D protein, human; 0/Calcium Channel Blockers; 0/Calcium Channels, L-Type; 0/Dihydropyridines; 3337-17-5/1,4-dihydropyridine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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