用遗传评分法预防补充Omega-3脂肪酸的潜在不良代谢影响

IF 2 4区 医学 Q3 GENETICS & HEREDITY
Maximilien Franck, J. de Toro-Martín, F. Guénard, I. Rudkowska, S. Lemieux, B. Lamarche, P. Couture, M. Vohl
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引用次数: 8

摘要

导读:据报道,食用长链omega-3多不饱和脂肪酸(n-3 PUFA)对健康有有益的影响,特别是通过降低血浆甘油三酯水平。尽管如此,也观察到伴随的胰岛素敏感性降低,但在受试者之间差异很大。在此,我们的目的是确定遗传背景在补充n-3 PUFA后胰岛素敏感性反应的个体间变异性中的重要性。方法:共有210名参与者完成了为期6周的n-3 PUFA补充,每天服用5克鱼油(提供1.9-2.2克二十碳五烯酸+ 1.1克二十二碳六烯酸)。胰岛素抵抗通过体内平衡模型评估(HOMA-IR)来估计,参与者根据补充n-3 PUFA后的HOMA-IR变化,与补充前的值相比,进一步分为高风险或低风险。使用包含4,301,331个单核苷酸多态性的HumanOmni-5-Quad BeadChips获得138名参与者的全基因组基因分型数据。在高风险和低风险参与者之间进行全基因组关联分析(GWAS)。人口研究分为训练(60%)和测试(40%)数据集,以评估通过风险等位基因数量总和构建的遗传风险评分(GRS)的预测准确性。结果:与初始值相比,补充n-3 PUFA后,32名参与者的HOMA-IR增加,被归类为高风险(23.2%),而其余受试者被归类为低风险(n = 106, 76.8%)。在GWAS关联阈值上,高风险和低风险参与者之间共有8个位点存在频率差异(p值<1 × 10-5)。在应用10倍交叉验证后,在测试数据集中,GRS显示与HOMA-IR增加的风险显著相关(OR = 3.16 [95% CI, 1.85-7.14]),预测精度为0.85,并解释了40%的HOMA-IR变化。结论:这些结果表明,遗传背景在补充n-3 PUFA后观察到的胰岛素敏感性反应的个体间变异性中起着相关作用。在补充n-3 PUFA后,有胰岛素敏感性降低风险的受试者可以使用基于基因的精确营养方法进行识别。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prevention of Potential Adverse Metabolic Effects of a Supplementation with Omega-3 Fatty Acids Using a Genetic Score Approach
Introduction: The consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) has been reported to have beneficial health effects, notably, by reducing plasma triglyceride levels. Nonetheless, a concomitant decrease in insulin sensitivity has also been observed, but is highly variable among subjects. Herein, we aimed to determine the importance of the genetic background in the interindividual variability of the insulin sensitivity response following an n-3 PUFA supplementation. Methods: A total of 210 participants completed a 6-week n-3 PUFA supplementation with 5 g/day of fish oil (providing 1.9–2.2 g of eicosapentaenoic acid + 1.1 g of docosahexaenoic acid). Insulin resistance was estimated by the homeostatic model assessment (HOMA-IR), and participants were further classified as high-risk or low-risk depending on their HOMA-IR change following the n-3 PUFA supplementation, as compared to pre-supplementation values. Genome-wide genotyping data were obtained for 138 participants using HumanOmni-5-Quad BeadChips containing 4,301,331 single nucleotide polymorphisms. A genome-wide association analysis (GWAS) was carried out between high-risk and low-risk participants. The population study was split into training (60%) and testing (40%) datasets to assess the predictive accuracy of a genetic risk score (GRS) constructed by summing the number of risk alleles. Results: Following the n-3 PUFA supplementation, 32 participants had increased HOMA-IR as compared to initial values and were classified as high risk (23.2%), whereas remaining subjects were classified as low risk (n = 106, 76.8%). A total of 8 loci had frequency differences between high-risk and low-risk participants at a suggestive GWAS association threshold (p value <1 × 10–5). After applying 10-fold cross validation, the GRS showed a significant association with the risk of increased HOMA-IR in the testing dataset (OR = 3.16 [95% CI, 1.85–7.14]), with a predictive accuracy of 0.85, and explained 40% of variation in HOMA-IR change. Conclusions: These results suggest that the genetic background has a relevant role in the interindividual variability observed in the insulin sensitivity response following an n-3 PUFA supplementation. Subjects being at risk of insulin sensitivity lowering following an n-3 PUFA supplementation may be identified using genetic-based precision nutrition approaches.
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来源期刊
Lifestyle Genomics
Lifestyle Genomics Agricultural and Biological Sciences-Food Science
CiteScore
4.00
自引率
7.70%
发文量
11
审稿时长
28 weeks
期刊介绍: Lifestyle Genomics aims to provide a forum for highlighting new advances in the broad area of lifestyle-gene interactions and their influence on health and disease. The journal welcomes novel contributions that investigate how genetics may influence a person’s response to lifestyle factors, such as diet and nutrition, natural health products, physical activity, and sleep, amongst others. Additionally, contributions examining how lifestyle factors influence the expression/abundance of genes, proteins and metabolites in cell and animal models as well as in humans are also of interest. The journal will publish high-quality original research papers, brief research communications, reviews outlining timely advances in the field, and brief research methods pertaining to lifestyle genomics. It will also include a unique section under the heading “Market Place” presenting articles of companies active in the area of lifestyle genomics. Research articles will undergo rigorous scientific as well as statistical/bioinformatic review to ensure excellence.
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