Zhou Sirui, Xiong Lan, Xie Pingxing, Ambalavanan Amirthagowri, Bourassa Cynthia V, Dionne-Laporte Alexandre, Spiegelman Dan, Turcotte Gauthier Maude, Henrion Edouard, Diallo Ousmane, Dion Patrick A, Rouleau Guy A
Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada; Département de médecine, Faculté de médecine, Université de Montréal, Montréal (Que), Canada.
Département de psychiatrie, Faculté de médecine, Université de Montréal, Montréal (Que), Canada; Centre de recherche, Institut universitaire en santé mentale de Montréal (Que), Canada.
PLoS One. 2015 May 26;10(5):e0128255. doi: 10.1371/journal.pone.0128255. eCollection 2015.
Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism.
Exome sequencing and SNP array genotyping were used to examine the genetic variations in the six genes encoding for the carnitine acyltransferases in 113 Nunavik Inuit individuals.
Altogether ten missense variants were found in genes CPT1A, CPT1B, CPT1C, CPT2 and CRAT, including three novel variants and one Inuit specific variant CPT1A p.P479L (rs80356779). The latter has the highest frequency (0.955) compared to other Inuit populations. We found that by comparison to Asians or Europeans, the Nunavik Inuit have an increased mutation burden in CPT1A, CPT2 and CRAT; there is also a high level of population differentiation based on carnitine acyltransferase gene variations between Nunavik Inuit and Asians.
The increased number and frequency of deleterious variants in these fatty acid metabolism genes in Nunavik Inuit may be the result of genetic adaptation to their diet and/or the extremely cold climate. In addition, the identification of these variants may help to understand some of the specific health risks of Nunavik Inuit.
努纳维克因纽特人（加拿大魁北克北部）居住在北极海岸沿线，数代以来，他们的日常能量摄入主要来源于动物脂肪。鉴于这种特殊的饮食结构，有人推测自然选择会导致与脂肪酸代谢相关基因出现特定于该人群的等位基因频率差异和独特变体。一组基因，即CPT1A、CPT1B、CPT1C、CPT2、CRAT和CROT，编码三种对脂肪酸氧化至关重要的肉碱酰基转移酶，脂肪酸氧化是其代谢过程中的关键步骤。
采用外显子组测序和单核苷酸多态性（SNP）阵列基因分型技术，对113名努纳维克因纽特人的六个编码肉碱酰基转移酶的基因进行遗传变异检测。
在CPT1A、CPT1B、CPT1C、CPT2和CRAT基因中总共发现了10个错义变体，包括3个新变体和1个因纽特人特有的变体CPT1A p.P479L（rs80356779）。与其他因纽特人群体相比后一个变体的频率最高（0.955）。我们发现，与亚洲人或欧洲人相比，努纳维克因纽特人在CPT1A、CPT2和CRAT基因中的突变负担增加；基于肉碱酰基转移酶基因变异，努纳维克因纽特人和亚洲人之间也存在高度的群体分化。
努纳维克因纽特人这些脂肪酸代谢基因中有害变体数量和频率的增加，可能是对其饮食和/或极端寒冷气候的遗传适应结果。此外，这些变体的识别可能有助于了解努纳维克因纽特人一些特定的健康风险。
