Effect of HMGCR Variant Alleles on Low-Density Lipoprotein Cholesterol-Lowering Response to Atorvastatin in Healthy Korean Subjects

The investigators quantified the relationship between the genetic polymorphism of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) and the low-density lipoprotein cholesterol (LDL-C)–lowering effects of atorvastatin in a prospective clinical study. Twenty-four healthy participants were groupe...

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Bibliographic Details
Published in:Journal of clinical pharmacology Vol. 52; no. 3; pp. 339 - 346
Main Authors: Chung, Jae Yong, Cho, Sung Kweon, Oh, Eun Sil, Lee, Dong Hwan, Lim, Lay Ahyoung, Jang, Seong Bok, Lee, Yoon Jung, Park, Kyungsoo, Park, Min Soo
Format: Journal Article
Language:English
Published: Oxford, UK Blackwell Publishing Ltd 01.03.2012
SAGE Publications
Wiley Subscription Services, Inc
Subjects:
Adult
Asian Continental Ancestry Group - genetics
Atorvastatin
Atorvastatin Calcium
Cholesterol
Cholesterol, LDL - blood
cholesterol-lowering drugs
Creatinine
Female
Gene polymorphism
Genotype
Heptanoic Acids - pharmacology
HMG-CoA reductase
Humans
Hydroxymethylglutaryl CoA Reductases - genetics
Hydroxymethylglutaryl CoA Reductases - metabolism
Hydroxymethylglutaryl-CoA reductase
Hypolipidemic Agents - pharmacology
Lipids
Lipoproteins
Low density lipoprotein
Male
pharmacogenetics
Pharmacokinetics
Polymorphism, Genetic
Pyrroles - pharmacology
Serum levels
Triglycerides
Young Adult
lipids
HMG-CoA reductase
cholesterol-lowering drugs
atorvastatin
pharmacogenetics
ISSN:0091-2700, 1552-4604, 1552-4604
Online Access:Get full text
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Summary:The investigators quantified the relationship between the genetic polymorphism of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) and the low-density lipoprotein cholesterol (LDL-C)–lowering effects of atorvastatin in a prospective clinical study. Twenty-four healthy participants were grouped into HMGCR rs3846662 GG (n = 13) and AA (n = 11) genotypes and given atorvastatin (20 mg/d) for 14 days. Serum levels of LDL-C, high-density lipoprotein cholesterol, total cholesterol, triglycerides, and creatinine kinase (CK) were measured before (day 1) and 7, 13, 14, 15, 16, 21, and 28 days after dosing initiation. Blood samples for pharmacokinetics were taken on days 14 through 16. The levels of LDL-C in the GG group were significantly higher than in the AA group at all observation times, with mean differences of 18% to 33% (P < .05). The area under the LDL-C–time curve and the minimum value of LDL-C in the GG group were 24% and 23% higher than in the AA group, respectively (P < .01). There was no significant difference in other lipids, CK, and pharmacokinetic parameters. The HMGCR rs3846662 GG genotype was quantitatively documented to be a significant determinant for higher LDL-C level in basal state and possibly in response to atorvastatin.
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ISSN:0091-2700
1552-4604
1552-4604
DOI:10.1177/0091270011398239