Chien Kuo-Liong, Lin Yen-Lin, Wen Hui-Chin, Lin Hsing-Pei, Yen Ching-Tzu, Lin Shu-Wha, Kao Jau-Tsuen
Institute of Preventive Medicine, School of Preventive Medicine, National Taiwan University, Taiwan.
Pharmacogenomics. 2009 Feb;10(2):267-76. doi: 10.2217/14622416.10.2.267.
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.
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.
Our results indicate that the LPL gene variant may cause triglyceride lowering after fibrate treatment among patients with hypertriglyceridemia.
关于高甘油三酯血症患者在接受贝特类药物治疗后，脂蛋白脂肪酶（LPL）和载脂蛋白基因簇（APOA1/C3/A5）的变异是否能显著降低甘油三酯水平，目前所知甚少。
我们调查了145例接受6个月贝特类药物治疗的高甘油三酯血症患者，这些基因的变异在贝特类药物治疗后是否能带来甘油三酯降低的反应。
总体甘油三酯水平从746.2mg/dl降至465.9mg/dl，甘油三酯降低的平均百分比为50.7±38.6%。共有两个多态性位点，即LPL内含子8 +483T>G和APOA1 +2169G>C，与显著的甘油三酯降低百分比相关。LPL对甘油三酯降低百分比的常见单倍型效应显著（p = 0.002），LPL单倍型解释的变异百分比为7.5%。与最常见的LPL单倍型相比，一个包含三个多态性位点的常见LPL单倍型与-45.40%的变化相关（p < 0.001），且出现不良反应的风险增加5.9倍（95%置信区间：1.11 - 31，p = 0.037）。
我们的结果表明，在高甘油三酯血症患者中，LPL基因变异可能导致贝特类药物治疗后甘油三酯降低。
