AJHG：有益脂肪或许能靶向miRNA降低心脏病风险

美国塔夫茨大学美国农业部人类营养老化研究中心(HNRCA)的科学家们已经发现了一个调节甘油三酸酯水平的新基因机制.这一途径可以保护一个基因变异的携带者对抗心血管疾病，特别是那些对多不饱和脂肪(PUFA)有更大摄入量的基因变异携带者.这一发现发表在 American Journal of Human Genetics杂志上，研究结果有助于开展能够改善公众健康和补充慢性疾病预防和治疗的基因特异的饮食策略。

作者分析了来自美国和欧洲十个流行病学研究的共2万7千多名男、女性参与者的数据，他们重点关注了单核苷酸多态性(SNP)rs13702，并发现一种小分子RNA——microRNA(miRNA)，影响了介导甘油三酯新陈代谢循环的一种酶——脂蛋白脂酶(lipoprotein lipase， LPL)的产生。

HNRCA营养基因组学实验室主任、资深科学家José M. Ordovás说：“我们可以看到，基因突变体携带者身上没有miRNA活性.“在大多数的受试者中，miRNA会粘附于mRNA上，减慢LPL的产生.没有这种干扰的话，带有突变体的人会有更多可用的LPL来分解过量的甘油三酯，防止它们在动脉血管中的沉积，最终预防动脉粥样硬化和其他心血管疾病的发生.”

作者还指出，基因突变携带者中甘油三酸酯水平的较低，而高密度脂蛋白(HDL)胆固醇（即健康胆固醇）的浓度较高.另外，突变体携带者如果摄入高水平的PUFA后，往往有更低的甘油三酸酯水平。

美国农业部农业科学研究院营养基因组学实验室的博士后助理Kris Richardson说：“基于这些数据，我们得出，当基因突变体携带者增加PUFA的摄入量后，可以更进一步地降低心血管疾病的发病风险.在我们数据的基础上，未来的研究可以调查人类培养细胞被PUFA处理后的影响，来确定PUFA是否可以通过这一特定的miRNA的识别介导LPL的水平。”

PUFA存在于一些食物中，如鲑鱼和植物油，它被认为是一种健康脂肪.最近美国膳食指南建议：如果有可能，可以用更有益的PUFA和单不饱和脂肪替换饱和脂肪。(生物谷Bioon.com)

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Gain-of-function lipoprotein lipase variant rs13702 modulates lipid traits through disruption of a microRNA-410 seed site.
Abstract
Genome-wide association studies (GWAS) have identified hundreds of genetic variants that are associated with lipid phenotypes. However, data supporting a functional role for these variants in the context of lipid metabolism are scarce. We investigated the association of the lipoprotein lipase (LPL) variant rs13702 with plasma lipids and explored its potential for functionality. The rs13702 minor allele had been predicted to disrupt a microRNA (miR) recognition element (MRE) seed site (MRESS) for the human microRNA-410 (miR-410). Furthermore, rs13702 is in linkage disequilibrium (LD) with several SNPs identified by GWAS. We performed a meta-analysis across ten cohorts of participants that showed a statistically significant association of rs13702 with triacylglycerols (TAG) (p = 3.18 × 10(-42)) and high-density lipoprotein cholesterol (HDL-C) (p = 1.35 × 10(-32)) with each copy of the minor allele associated with 0.060 mmol/l lower TAG and 0.041 mmol/l higher HDL-C. Our data showed that an LPL 3' UTR luciferase reporter carrying the rs13702 major T allele was reduced by 40% in response to a miR-410 mimic. We also evaluated the interaction between intake of dietary fatty acids and rs13702. Meta-analysis demonstrated a significant interaction between rs13702 and dietary polyunsaturated fatty acid (PUFA) with respect to TAG concentrations (p = 0.00153), with the magnitude of the inverse association between dietary PUFA intake and TAG concentration showing -0.007 mmol/l greater reduction. Our results suggest that rs13702 induces the allele-specific regulation of LPL by miR-410 in humans. This work provides biological and potential clinical relevance for previously reported GWAS variants associated with plasma lipid phenotypes.