Schoenborn Veit, Heid Iris M, Vollmert Caren, Lingenhel Arno, Adams Ted D, Hopkins Paul N, Illig Thomas, Zimmermann Robert, Zechner Rudolf, Hunt Steven C, Kronenberg Florian
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular/Clinical Pharmacology, Innsbruck Medical University, Schöpfstrasse 41, A-6020 Innsbruck, Austria.
Diabetes. 2006 May;55(5):1270-5. doi: 10.2337/db05-1498.
Adipose triglyceride lipase (ATGL) was recently described to predominantly perform the initial step in triglyceride hydrolysis and therefore seems to play a pivotal role in the lipolytic catabolism of stored fat in adipose tissue. In the first study investigating genetic variations within the ATGL gene in humans, 12 polymorphisms identified via sequencing and database search were studied in 2,434 individuals of European ancestry from Utah. These polymorphisms and their haplotypes were analyzed in subjects not taking diabetes medication for association with plasma free fatty acids (FFAs) as primary analysis, as well as triglycerides and glucose as a secondary analysis (n = 1,701, 2,193, or 2,190, respectively). Furthermore, type 2 diabetes (n = 342 of 2,434) was analyzed as an outcome. FFA concentrations were significantly associated with several single nucleotide polymorphisms (SNPs) of ATGL (P values from 0.015 to 0.00003), consistent with additive inheritance. The pattern was similar when considering triglyceride concentrations. Furthermore, two SNPs showed associations with glucose levels (P < 0.00001) and risk of type 2 diabetes (P < 0.05). Haplotype analysis supported and extended the shown SNP association analyses. These results complement previous findings of functional studies in mammals and elucidate a potential role of ATGL in pathways involved in components of the metabolic syndrome.
脂肪甘油三酯脂肪酶（ATGL）最近被描述为主要在甘油三酯水解的初始步骤中发挥作用，因此似乎在脂肪组织中储存脂肪的脂解分解代谢中起关键作用。在第一项研究人类ATGL基因内遗传变异的研究中，对来自犹他州的2434名欧洲血统个体中通过测序和数据库搜索鉴定出的12种多态性进行了研究。这些多态性及其单倍型在未服用糖尿病药物的受试者中进行分析，以与血浆游离脂肪酸（FFA）的关联作为主要分析，以及甘油三酯和葡萄糖作为次要分析（分别为n = 1701、2193或2190）。此外，将2型糖尿病（2434例中的342例）作为结果进行分析。FFA浓度与ATGL的几个单核苷酸多态性（SNP）显著相关（P值从0.015至0.00003），符合加性遗传。考虑甘油三酯浓度时，模式相似。此外，两个SNP与血糖水平（P < 0.00001）和2型糖尿病风险（P < 0.05）相关。单倍型分析支持并扩展了所示的SNP关联分析。这些结果补充了先前在哺乳动物中进行的功能研究的发现，并阐明了ATGL在代谢综合征组分相关途径中的潜在作用。
