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Genetic study of the Arctic CPT1A variant suggests that its effect on fatty acid levels is modulated by traditional Inuit diet.
European Journal of Human Genetics ( IF 3.7 ) Pub Date : 2020-06-19 , DOI: 10.1038/s41431-020-0674-0
Ninna Senftleber 1, 2, 3 , Marit Eika Jørgensen 2 , Emil Jørsboe 1 , Fumiaki Imamura 3 , Nita Gandhi Forouhi 3 , Christina Lytken Larsen 4 , Peter Bjerregaard 4 , Torben Hansen 5, 6 , Anders Albrechtsen 1
Affiliation  

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.



中文翻译:


对北极 CPT1A 变体的遗传研究表明,其对脂肪酸水平的影响受到传统因纽特人饮食的调节。



最近的几项研究发现,北极人群祖先的肉毒碱棕榈酰转移酶 1A ( CPT1A ) 基因最近被选择的迹象可能是由于他们的传统饮食所致。 CPT1A 参与脂肪酸运输,已知会影响因纽特人的循环脂肪酸谱,富含海洋动物的独特传统饮食也会影响循环脂肪酸谱。我们的目的是通过分析变体与传统因纽特人饮食之间的潜在相互作用,评估哪些脂肪酸可能驱动了CPT1A中 c.1436C>T (p.(Pro479Leu)) 变体 rs80356779 的选择。我们纳入了 3005 名居住在格陵兰岛的全基因组基因型个体,并对他们的血细胞膜脂肪酸水平进行了测量。 25 种传统食品的消费量以占总能量摄入量的百分比表示。我们测试了CPT1A × 传统饮食的相互作用,同时考虑了相关性和混合性。据估计,增加传统饮食的摄入量会减弱 479L 对 20:3 omega-6 水平的影响 ( p = 0.000399),但会增加该变体对 22:5 omega-3 水平的影响 ( p = 0.000963)。与传统饮食摄入量低(10% 百分位)的个体相比,479L 对 22:5 omega-3 的影响在传统饮食摄入量高(90% 百分位)的个体中增加了一倍多。在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,传统饮食和血细胞脂肪酸组成之间的关联受到CPT1A基因型或连锁不平衡的其他变异的影响,并支持 omega-3 脂肪酸可能对于适应北极饮食很重要的假设。

更新日期:2020-06-19
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