Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, and Institute of Food and Health, University College Dublin, Ireland.
J Lipid Res. 2010 Jul;51(7):1793-800. doi: 10.1194/jlr.M003046. Epub 2010 Feb 22.
Long-chain acyl CoA synthetase 1 (ACSL1) plays an important role in fatty acid metabolism and triacylglycerol (TAG) synthesis. Disturbance of these pathways may result in dyslipidemia and insulin resistance, hallmarks of the metabolic syndrome (MetS). Dietary fat is a key environmental factor that may interact with genetic determinants of lipid metabolism to affect MetS risk. We investigated the relationship between ACSL1 polymorphisms (rs4862417, rs6552828, rs13120078, rs9997745, and rs12503643) and MetS risk and determined potential interactions with dietary fat in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1,754). GG homozygotes for rs9997745 had increased MetS risk {odds ratio (OR) 1.90 [confidence interval (CI) 1.15, 3.13]; P = 0.01}, displayed elevated fasting glucose (P = 0.001) and insulin concentrations (P = 0.002) and increased insulin resistance (P = 0.03) relative to the A allele carriers. MetS risk was modulated by dietary fat, whereby the risk conferred by GG homozygosity was abolished among individuals consuming either a low-fat (<35% energy) or a high-PUFA diet (>5.5% energy). In conclusion, ACSL1 rs9997745 influences MetS risk, most likely via disturbances in fatty acid metabolism, which was modulated by dietary fat consumption, particularly PUFA intake, suggesting novel gene-nutrient interactions.
长链酰基辅酶 A 合成酶 1（ACSL1）在脂肪酸代谢和三酰基甘油（TAG）合成中发挥重要作用。这些途径的紊乱可能导致血脂异常和胰岛素抵抗，这是代谢综合征（MetS）的标志。膳食脂肪是一种关键的环境因素，可能与脂质代谢的遗传决定因素相互作用，影响 MetS 的风险。我们研究了 ACSL1 多态性（rs4862417、rs6552828、rs13120078、rs9997745 和 rs12503643）与 MetS 风险之间的关系，并确定了它们与膳食脂肪之间的潜在相互作用，这项研究是在 MetS 病例和匹配对照的 LIPGENE-SU.VI.MAX 研究中进行的（n = 1754）。rs9997745 的 GG 纯合子患 MetS 的风险增加{比值比（OR）1.90[置信区间（CI）1.15,3.13]; P = 0.01}，与 A 等位基因携带者相比，空腹血糖（P = 0.001）和胰岛素浓度（P = 0.002）升高，胰岛素抵抗增加（P = 0.03）。膳食脂肪调节了 MetS 的风险，其中在摄入低脂肪（<35%能量）或高多不饱和脂肪酸（PUFA）（>5.5%能量）饮食的个体中，GG 纯合子所带来的风险被消除。总之，ACSL1 rs9997745 影响 MetS 风险，很可能是通过脂肪酸代谢紊乱，而这种紊乱受膳食脂肪的消耗，特别是 PUFA 摄入的调节，提示了新的基因-营养相互作用。
