Kulkarni Hemant, Mamtani Manju, Wong Gerard, Weir Jacquelyn M, Barlow Christopher K, Dyer Thomas D, Almasy Laura, Mahaney Michael C, Comuzzie Anthony G, Duggirala Ravindranath, Meikle Peter J, Blangero John, Curran Joanne E
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, 78520, USA.
Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
BMC Genet. 2017 May 19;18(1):48. doi: 10.1186/s12863-017-0515-5.
Differential plasma concentrations of circulating lipid species are associated with pathogenesis of type 2 diabetes (T2D). Whether the wide inter-individual variability in the plasma lipidome contributes to the genetic basis of T2D is unknown. Here, we investigated the potential overlap in the genetic basis of the plasma lipidome and T2D-related traits.
We used plasma lipidomic data (1202 pedigreed individuals, 319 lipid species representing 23 lipid classes) from San Antonio Family Heart Study in Mexican Americans. Bivariate trait analyses were used to estimate the genetic and environmental correlation of all lipid species with three T2D-related traits: risk of T2D, presence of prediabetes and homeostatic model of assessment - insulin resistance. We found that 44 lipid species were significantly genetically correlated with one or more of the three T2D-related traits. Majority of these lipid species belonged to the diacylglycerol (DAG, 17 species) and triacylglycerol (TAG, 17 species) classes. Six lipid species (all belonging to the triacylglycerol class and containing palmitate at the first position) were significantly genetically correlated with all the T2D-related traits.
Our results imply that: a) not all plasma lipid species are genetically informative for T2D pathogenesis; b) the DAG and TAG lipid classes partially share genetic basis of T2D; and c) 1-palmitate containing TAGs may provide additional insights into the genetic basis of T2D.
循环脂质种类的血浆浓度差异与2型糖尿病(T2D)的发病机制相关。血浆脂质组中个体间的广泛变异性是否有助于T2D的遗传基础尚不清楚。在此,我们研究了血浆脂质组和T2D相关性状的遗传基础中潜在的重叠部分。
我们使用了来自圣安东尼奥墨西哥裔美国人家庭心脏研究的血浆脂质组数据(1202名有谱系的个体,代表23类脂质的319种脂质种类)。采用双变量性状分析来估计所有脂质种类与三个T2D相关性状的遗传和环境相关性:T2D风险、糖尿病前期的存在以及评估胰岛素抵抗的稳态模型。我们发现44种脂质种类与三个T2D相关性状中的一个或多个显著遗传相关。这些脂质种类中的大多数属于二酰基甘油(DAG,17种)和三酰基甘油(TAG,17种)类别。六种脂质种类(均属于三酰基甘油类别且在第一位含有棕榈酸酯)与所有T2D相关性状显著遗传相关。
我们的结果表明:a)并非所有血浆脂质种类在T2D发病机制方面都具有遗传信息;b)DAG和TAG脂质类别部分共享T2D的遗传基础;c)含有1-棕榈酸酯的TAGs可能为T2D的遗传基础提供更多见解。