Associations between Common Genetic Polymorphisms in Angiopoietin-Like Proteins 3 and 4 and Lipid Metabolism and Adiposity in European Adolescents and Adults
Associations between Common Genetic Polymorphisms in Angiopoietin-Like Proteins 3 and 4 and Lipid Metabolism and Adiposity in European Adolescents and Adults
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DOI：
10.1210/jc.2009-0769
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发表时间：
2009-12-01
影响因子：
5.8
通讯作者：
Meirhaeghe, Aline
中科院分区：
文献类型：
--
作者：
Legry, Vanessa;Bokor, Szilvia;Meirhaeghe, Aline
背景：血浆血管生成素样蛋白（ANGPTL）作为内分泌因子作用于靶组织。由于ANGPTL 3和ANGPTL 4在小鼠的脂质代谢和肥胖调节中起重要作用，我们假设ANGPTL 3和ANGPTL 4基因位点的遗传变异可能影响人类的脂质代谢和脂肪沉积。目的：本研究的目的是检查ANGPTL 3和ANGPTL 4基因多态性与青少年和成人样本中代谢表型之间的关联。设计和参与者：两项独立的基于人群的研究，一项由1144名青少年组成（平均年龄：14.8 ± 1.4岁），来自9个欧洲国家（HELENA研究）和另一项由1155名成年人组成的研究（年龄范围，35-65岁）来自法国北方（MONICA里尔研究），对一个ANGPTL 3多态性和四个ANGPTL 4多态性进行基因分型。ANGPTL 3 rs 11207997多态性在这两个青少年中，（次要等位基因频率，0.32）与较低的血浆HDL-胆固醇和载脂蛋白A-I水平相关（P = 0.0004，P = 0.00006）和成人（P = 0.03，P = 0.02）。ANGPTL 4 rs 4076317多态性（次要等位基因频率，0.29）与较高的体脂百分比相关（P = 0.02）青少年和较高的腰臀比（与过氧化物酶体增殖物激活受体γ Pro 12 Ala多态性相互作用）结论：ANGPTL 3在青少年时期就参与了HDL-胆固醇代谢。我们的数据还表明ANGPTL 4多态性与体脂之间可能存在关联，但这些发现需要重复。（临床内分泌代谢杂志94：5070-5077，2009）
Context: Plasma-borne angiopoietin-like proteins (ANGPTL) act as endocrine factors on their target tissues. Because ANGPTL3 and ANGPTL4 play important roles in lipid metabolism and the regulation of adiposity in mice, we hypothesized that genetic variability at the ANGPTL3 and ANGPTL4 genes loci might influence lipid metabolism and fat deposition in humans.Objective: The aim of the study was to examine the association between ANGPTL3 and ANGPTL4 genetic polymorphisms and metabolic phenotypes in adolescent and adult samples.Design and Participants: Two independent population-based studies, one composed of 1144 adolescents (mean age, 14.8 +/- 1.4 yr) from nine European countries (the HELENA study) and the other composed of 1155 adults (age range, 35-65 yr) from Northern France (the MONICA Lille study), were genotyped for one ANGPTL3 polymorphism and four ANGPTL4 polymorphisms.Results: The ANGPTL3 rs11207997 polymorphism (minor allele frequency, 0.32) was associated with lower plasma HDL-cholesterol and apolipoprotein A-I levels in both adolescents (P = 0.0004, P = 0.00006, respectively) and adults (P = 0.03, P = 0.02, respectively). The ANGPTL4 rs4076317 polymorphism (minor allele frequency, 0.29) was associated with a higher percentage of body fat (P = 0.02) in adolescents and a higher waist-to-hip ratio (in interaction with the peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism) in adults (P = 0.0004).Conclusion: The present study underlines the role of ANGPTL3 in HDL-cholesterol metabolism as early as in adolescence. Our data also suggest possible associations between ANGPTL4 polymorphisms and body fat, but these findings require replication. (J Clin Endocrinol Metab 94: 5070-5077, 2009)