Rudkowska Iwona, Guénard Frédéric, Julien Pierre, Couture Patrick, Lemieux Simone, Barbier Olivier, Calder Philip C, Minihane Anne Marie, Vohl Marie-Claude
Institute of Nutrition and Functional Foods and Laval University, Quebec, Canada Endocrinology and Nephrology and CHU de Québec Research Center, Quebec, Canada.
Endocrinology and Nephrology and CHU de Québec Research Center, Quebec, Canada.
J Lipid Res. 2014 Jul;55(7):1245-53. doi: 10.1194/jlr.M045898. Epub 2014 May 19.
Studies have shown a large interindividual variability in plasma TG response to long-chain n-3 PUFA supplementation, which may likely be attributable to genetic variability within the populations studied. The objective is to compare the frequency of SNPs in a genome-wide association study between responders (reduction in plasma TG levels ≥0.01 mM) and nonresponders (increase in plasma TG of ≥0 mM) to supplementation. Genomic DNA from 141 subjects who completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil daily (1.9-2.2 g EPA and 1.1 g DHA daily) were genotyped on Illumina HumanOmni-5-QuadBeadChip. Thirteen loci had frequency differences between responders and nonresponders (P < 1 × 10(-5)), including SNPs in or near IQCJ-SCHIP1, MYB, NELL1, NXPH1, PHF17, and SLIT2 genes. A genetic risk score (GRS) was constructed by summing the number of risk alleles. This GRS explained 21.53% of the variation in TG response to n-3 PUFA supplementation when adjusted for age, sex, and BMI (P = 0.0002). Using Fish Oil Intervention and Genotype as a replication cohort, the GRS was able to explain 2% of variation in TG response when adjusted. In conclusion, subjects who decrease their plasma TG levels following n-3 PUFA supplementation may have a different genetic profile than individuals who do not respond.
研究表明，血浆甘油三酯（TG）对长链n-3多不饱和脂肪酸（PUFA）补充剂的反应存在很大的个体间差异，这可能归因于所研究人群中的基因变异。目的是在全基因组关联研究中比较对补充剂有反应者（血浆TG水平降低≥0.01 mM）和无反应者（血浆TG升高≥0 mM）的单核苷酸多态性（SNP）频率。对141名受试者的基因组DNA进行基因分型，这些受试者先完成了2周的导入期，随后每天补充5克鱼油（每天1.9 - 2.2克二十碳五烯酸（EPA）和1.1克二十二碳六烯酸（DHA）），使用的是Illumina HumanOmni-5-QuadBeadChip芯片。有13个位点在反应者和无反应者之间存在频率差异（P < 1×10⁻⁵），包括IQCJ - SCHIP1、MYB、NELL1、NXPH1、PHF17和SLIT2基因内或附近的SNP。通过对风险等位基因数量求和构建了一个遗传风险评分（GRS）。在调整年龄、性别和体重指数（BMI）后，该GRS解释了n-3 PUFA补充剂对TG反应中21.53%的变异（P = 0.0002）。以鱼油干预和基因型作为复制队列，调整后GRS能够解释TG反应中2%的变异。总之，n-3 PUFA补充后血浆TG水平降低的受试者可能与无反应个体具有不同的基因特征。
