Department of Biology, Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark.
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
Eur J Hum Genet. 2020 Nov;28(11):1592-1601. doi: 10.1038/s41431-020-0674-0. Epub 2020 Jun 19.
Several recent studies have found signs of recent selection on the carnitine palmitoyl-transferase 1A (CPT1A) gene in the ancestors of Arctic populations likely as a result of their traditional diet. CPT1A is involved in fatty acid transportation and is known to affect circulating fatty acid profiles in Inuit as does the unique traditional diet rich in marine animals. We aimed to assess which fatty acids may have driven the selection of rs80356779, a c.1436C>T (p.(Pro479Leu)) variant in CPT1A, by analyzing a potential interaction between the variant and traditional Inuit diet. We included 3005 genome-wide genotyped individuals living in Greenland, who had blood cell membrane fatty acid levels measured. Consumption of 25 traditional food items was expressed as percentage of total energy intake. We tested for CPT1A × traditional diet interaction while taking relatedness and admixture into account. Increasing intakes of traditional diet was estimated to attenuate the effect of 479L on 20:3 omega-6 levels (p = 0.000399), but increase the effect of the variant on 22:5 omega-3 levels (p = 0.000963). The 479L effect on 22:5 omega-3 more than doubled in individuals with a high intake of traditional diet (90% percentile) compared with individuals with a low intake (10% percentile). Similar results were found when assessing interactions with marine foods. Our results suggest that the association between traditional diet and blood cell fatty acid composition is affected by the CPT1A genotype, or other variants in linkage disequilibrium, and support the hypothesis that omega-3 fatty acids may have been important for adaptation to the Arctic diet.
几项最近的研究在北极人群的祖先中发现了肉碱棕榈酰转移酶 1A（CPT1A）基因的近期选择迹象，这可能是由于他们传统的饮食。CPT1A 参与脂肪酸的运输，已知会影响因纽特人的循环脂肪酸谱，而富含海洋动物的独特传统饮食也是如此。我们旨在通过分析该变体与传统因纽特饮食之间的潜在相互作用，评估哪些脂肪酸可能导致了 CPT1A 中 rs80356779 的选择，该变体为 c.1436C>T（p.（Pro479Leu））变体。我们纳入了 3005 名居住在格陵兰的全基因组基因分型个体，他们的血细胞膜脂肪酸水平进行了测量。传统食物的摄入量表示为总能量摄入的百分比。我们在考虑亲缘关系和混合的情况下，测试了 CPT1A × 传统饮食的相互作用。增加传统饮食的摄入量估计会减弱 479L 对 20:3 欧米伽-6 水平的影响（p = 0.000399），但会增加该变体对 22:5 欧米伽-3 水平的影响（p = 0.000963）。与低摄入量（10%百分位数）个体相比，在高摄入量（90%百分位数）个体中，479L 对 22:5 欧米伽-3 的影响增加了一倍以上。当评估与海洋食品的相互作用时，也发现了类似的结果。我们的结果表明，传统饮食与血细胞脂肪酸组成之间的关联受 CPT1A 基因型或其他连锁不平衡的变体的影响，并支持了 omega-3 脂肪酸可能对适应北极饮食很重要的假说。
