Associations of Genetic Polymorphisms with Lipid Lowering Effects of Statin Therapy
Date Issued
2008
Date
2008
Author(s)
Lo, Chen-Hsu
Abstract
The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, play an important role in the management of hypercholesterolemia and reduction of cardiovascular risks. It has been shown that genetic polymorphisms may contribute to variations of the response to statin therapy. However, most study population comprised Caucasians or African-Americans and the data obtained from Asians are scarce. This study aims to evaluate the association between genetic polymorphisms and atorvastatin (ATV), rosuvastatin (RSV) as well, among Asians in Taiwan.he DNA of 132 hypercholestemic individuals treated with ATV 10 mg/day or RSV 10 mg/day were analyzed for 48 SNPs within genes related to lipid metabolism, including ABCA1、ABCG2、ABCG5/G8、FDFT1、HMGCR、LDLR、CETP and genes related to drug disposition, including CYP2C9/19、CYP2D6、CYP3A4/5、ABCB1、SLCO1B1. The variations in genetic polymorphisms were further examined for associations with changes of levels of triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, non-HDL cholesterol and low density lipoprotein (LDL) cholesterol, and with the ratio of TG/HDL and TC/HDL.NP site rs5929 and rs4508523 in gene coding for LDLR were significantly associated to the variation of ATV and RSV therapy, respectively. Among those treated with ATV, individuals with more than one copy of T allele at rs5929 in LDLR had greater reduction in LDL cholesterol level (-68.42±19.57 mg/dL vs -57.64±21.85 mg/dL, p=0.029). Within those treated with RSV, individuals with more than one copy of C allele had greater reduction in level of TC (-93.45±31.97 mg/dL vs -62.17±48.15 mg/dL, p=0.035), TC/HDL (-1.83±0.66 vs-1.14±1.00, p=0.029), and non-HDL cholesterol (-90.78±29.08 mg/dL vs -59.67±46.91 mg/dL, p=0.025). Several SNPs were found to be related to the reduction of lipid levels, but the associations were no longer statistically significant after correction with baseline lipid levels.his study concluded that genetic polymorphisms in LDLR may affect the response of ATV and RSV. Results of this study need to be further validated in a larger, independent and prospective study.
Subjects
HMG-CoA reductase inhibitor
single nucleotide polymorphism
cholesterol
File(s)![Thumbnail Image]()
Loading...
Name
ntu-97-R94451007-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):fe94792637aa1f9f5925a9279cc145a2