Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia.
Laboratory for Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade 11000, Serbia.
Nutr Res. 2020 Nov;83:49-62. doi: 10.1016/j.nutres.2020.08.010. Epub 2020 Aug 22.
Polymorphisms in FADS genes are associated with plasma long-chain polyunsaturated fatty acids (LC-PUFA) and modulate omega-6/omega-3 balance. We hypothesized that the FADS2 gene variants will be associated with lower product-to-precursor ratio in the fatty acid metabolic pathways. Thus, we explored FADS2 rs174593, rs174616, and rs174576 effects on plasma phospholipid fatty acid profile, markers of desaturase activities, and risk factors in a sample of apparently healthy Serbian adults. Food and nutrient intake data were compiled through 24 h recalls. Plasma phospholipid fatty acid content was assessed by gas-chromatography. Estimated desaturase activities were calculated as conversion rates towards LC-PUFA in omega-6 pathway. During the selection of FADS2 polymorphisms, we accounted for their positional and functional aspect. Genotyping was performed by Real-Time PCR. Multivariable-adjusted general linear and hierarchical regression models were applied. Study subjects (mean age = 40 ± 7 years, 70% who were overweight) had a median dietary omega-6/omega-3 ratio of 16.29. Alternative allele frequencies were 33%, 36%, and 51% for rs174593, rs174576, and rs174616, respectively. Addition of FADS2 alternative alleles was associated with lower plasma arachidonic acid (AA, C20:4 n-6, P < .001) and estimated desaturase-5 activity (P < .001), irrespective of gender, age, daily polyunsaturated/saturated fatty acid intake, and obesity. The rs174576 association with AA withstood multiple testing and additional adjustments for other variants (multivariable-adjusted β = -1.14 [95% CI: -2.25, -0.43]). None of the variants was associated with dietary intake, serum lipids, or obesity. We observed inverse associations between FADS2 variants and plasma AA but not omega-3 fatty acids in Serbian subjects, with rs174576 exhibiting the strongest relation.
FADS 基因多态性与血浆长链多不饱和脂肪酸 (LC-PUFA) 有关，并调节 ω-6/ω-3 平衡。我们假设 FADS2 基因变异与脂肪酸代谢途径中的产物-前体比例降低有关。因此，我们在一个来自塞尔维亚的健康成年人样本中探索了 FADS2 rs174593、rs174616 和 rs174576 对血浆磷脂脂肪酸谱、去饱和酶活性标志物和危险因素的影响。通过 24 小时回忆收集食物和营养素摄入量数据。通过气相色谱法评估血浆磷脂脂肪酸含量。通过 LC-PUFA 在 ω-6 途径中的转化率计算估计的去饱和酶活性。在选择 FADS2 多态性时，我们考虑了它们的位置和功能方面。通过实时 PCR 进行基因分型。应用多元调整的一般线性和层次回归模型。研究对象（平均年龄为 40 ± 7 岁，70%超重）的饮食 ω-6/ω-3 比值中位数为 16.29。rs174593、rs174576 和 rs174616 的替代等位基因频率分别为 33%、36%和 51%。无论性别、年龄、每日多不饱和/饱和脂肪酸摄入量和肥胖情况如何，添加 FADS2 替代等位基因与较低的血浆花生四烯酸 (AA，C20:4 n-6，P <.001) 和估计的去饱和酶-5 活性 (P <.001) 相关。rs174576 与 AA 的关联在多次测试中仍然存在，并且在其他变体中进行了额外的调整（多变量调整后的β= -1.14 [95%CI：-2.25，-0.43]）。没有一个变体与饮食摄入、血清脂质或肥胖有关。我们在塞尔维亚受试者中观察到 FADS2 变体与血浆 AA 之间的反比关系，但与 ω-3 脂肪酸无关，其中 rs174576 表现出最强的关系。
