Common sequence variant in lipoprotein lipase gene conferring triglyceride response to fibrate treatment

被引:5
作者
Chien, K-L
Lin, Y-L
Wen, H-C
Lin, H-P
Yen, C-T
Lin, S-W
Kao, J-T
机构
[1] Institute of Preventive Medicine, School of Preventive Medicine, National Taiwan University, Taipei
[2] Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei
[3] Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Chung-San South Road
关键词
fibrate; hypertriglyceridemia; LPL gene; pharmacogenomics; triglyceride; TYPE-2; DIABETES-MELLITUS; CORONARY-ARTERY-DISEASE; MICRONIZED FENOFIBRATE; APOLIPOPROTEIN-E; HYPERTRIGLYCERIDEMIA; POLYMORPHISM; MUTATIONS; DISEQUILIBRIUM; ATORVASTATIN; ASSOCIATIONS;
D O I
10.2217/14622416.10.2.267
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims: Little is known about whether the variations in the lipoprotein lipase (LPL) and apolipoprotein gene cluster (APOA1/C3/A5) confer appreciable triglyceride lowering after fibrate treatment among patients with hypertriglyceridemia. Materials & methods: We investigated whether variations in these genes confer a triglyceride lowering response after fibrate treatment among 145 patients with hypertriglyceridemia receiving 6 months of fibrate treatment. Results: Overall triglycerides decreased from 746.2 mg/dl to 465.9 mg/dl and the mean percentage of triglyceride lowering was 50.7 +/- 38.6%. A total of two polymorphisms, LPL IVS8 +483T>G and APOA1 +2169G>C, were associated with a significant percentage of triglyceride lowering. Common haplotype effects of LPL on the triglyceride lowering percentage were significant (p = 0.002) and the percentage of variance explained by the LPL haplotype was 7.5%. One common LPL haplotype encompassing three polymorphisms was associated with a -45.40% change (p < 0.001) and risk of a 5.9-fold risk for developing a poor response (95% confidence interval: 1.11-31, p = 0.037), compared with the most frequent LPL haplotype. Conclusion: Our results indicate that the LPL gene variant may cause triglyceride lowering after fibrate treatment among patients with hypertriglyceridemia.
引用
收藏
页码:267 / 276
页数:10
相关论文
共 31 条
[1]   High-maintenance proteins and hypertriglyceridemia [J].
Attie, Alan D. .
NATURE GENETICS, 2007, 39 (12) :1424-1425
[2]  
Auwerx J, 1996, J Atheroscler Thromb, V3, P81
[3]   Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons [J].
Beigneux, Anne P. ;
Davies, Brandon S. J. ;
Gin, Peter ;
Weinstein, Michael M. ;
Farber, Emily ;
Qiao, Xin ;
Peale, Franklin ;
Bunting, Stuart ;
Walzem, Rosemary L. ;
Wong, Jinny S. ;
Blaner, William S. ;
Ding, Zhi-Ming ;
Melford, Kristan ;
Wongsiriroj, Nuttaporn ;
Shu, Xiao ;
de Sauvage, Fred ;
Ryan, Robert O. ;
Fong, Loren G. ;
Bensadoun, Andre ;
Young, Stephen G. .
CELL METABOLISM, 2007, 5 (04) :279-291
[4]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[5]   Effect of apolipoprotein E, peroxisome proliferator-activated receptor alpha and lipoprotein lipase gene mutations on the ability of fenofibrate to improve lipid profiles and reach clinical guideline targets among hypertriglyceridemic patients [J].
Brisson, D ;
Ledoux, K ;
Bossé, Y ;
St-Pierre, J ;
Julien, P ;
Perron, P ;
Hudson, TJ ;
Vohl, MC ;
Gaudet, D .
PHARMACOGENETICS, 2002, 12 (04) :313-320
[6]   Genetic variation in the hepatic lipase gene is associated with combined hyperlipidemia, plasma lipid concentrations, and lipid-lowering drug response [J].
Cenarro, A ;
Artieda, M ;
Gonzalvo, C ;
Meriño-Ibarra, E ;
Arístegui, R ;
Gañán, A ;
Díaz, C ;
Sol, JM ;
Pocoví, M ;
Civeira, F .
AMERICAN HEART JOURNAL, 2005, 150 (06) :1154-1162
[7]   Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease [J].
Chen, Qi ;
Razzaghi, Hamid ;
Demirci, F. Yesim ;
Kamboh, M. Ilyas .
ATHEROSCLEROSIS, 2008, 200 (01) :102-108
[8]   APOA1/C3/A5 haplotype and risk of hypertriglyceridemia in Taiwanese [J].
Chien, Kuo-Liong ;
Fang, Woei-Horng ;
Wen, Hui-Chin ;
Lin, Hsing-Pei ;
Lin, Yen-Lin ;
Lin, Shu-Wha ;
Wu, June-Hsieh ;
Kao, Jau-Tsuen .
CLINICA CHIMICA ACTA, 2008, 390 (1-2) :56-62
[9]   The effect of apolipoprotein E polymorphism on the response to lipid-lowering treatment with atorvastatin or fenofibrate [J].
Christidis, Dimitrios S. ;
Liberopoulos, Evangelos N. ;
Kakafika, Anna I. ;
Miltiadous, George A. ;
Cariolou, Marios ;
Ganotakis, Emmanuel S. ;
Mikhailidis, Dimitri P. ;
Elisaf, Moses S. .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS, 2006, 11 (03) :211-221
[10]   A COMPARISON OF LINKAGE DISEQUILIBRIUM MEASURES FOR FINE-SCALE MAPPING [J].
DEVLIN, B ;
RISCH, N .
GENOMICS, 1995, 29 (02) :311-322