The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.
The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.
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DOI：
10.1093/hmg/ddac153
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发表时间：
2022-11-28
影响因子：
3.5
通讯作者：
中科院分区：
文献类型：
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尽管很早就引起了人们的兴趣，但将脂肪酸与心血管疾病（CVD）联系起来的证据仍然存在争议。我们使用孟德尔随机化方法，在多达 1 153 768 名欧洲人（最多 123 668 例）和 212 453 名东亚人（最多 29 319 例）血统个体中探讨了多不饱和 (PUFA) 和单不饱和 (MUFA) 脂肪酸生物合成在几个 CVD 终点病因中的作用。作为工具，我们选择了映射到 PUFA（即 FADS1/2 和 ELOVL2）和 MUFA（即 SCD）生物合成中具有众所周知作用的基因的单核苷酸多态性。我们的研究结果表明，较高的 PUFA 生物合成率（由 FADS1/2 附近的 rs174576 代表）与多种 CVD 的较高几率相关，特别是缺血性中风、外周动脉疾病和静脉血栓栓塞，而较高的 MUFA 生物合成率（由 SCD 附近的 rs603424 代表）与较低的冠状动脉疾病几率相关。 欧洲人。对于东亚人来说，结果尚不清楚，因为大多数效果估计都不精确。通过三角测量多种方法（即单/多变量孟德尔随机化、全表型扫描、遗传共定位和同胞内分析），我们的结果与较高的低密度脂蛋白（LDL）胆固醇（可能还有葡萄糖）相一致，这是较高的PUFA生物合成率的下游效应。我们的研究结果表明，PUFA 和 MUFA 生物合成与 CVD 的病因有关，并表明 LDL 胆固醇是 PUFA 生物合成和 CVD 风险之间的潜在中介特征。
Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1 153 768 European (maximum 123 668 cases) and 212 453 East Asian (maximum 29 319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.
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影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
影响因子：
3.5
作者：
Dorajoo, Rajkumar;Sun, Ye;Friedlander, Yechiel
通讯作者：
Friedlander, Yechiel
DOI：
10.1136/bmj.e6698
发表时间：
2012-10-30
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Chowdhury R;Stevens S;Gorman D;Pan A;Warnakula S;Chowdhury S;Ward H;Johnson L;Crowe F;Hu FB;Franco OH
通讯作者：
Franco OH
影响因子：
3.5
作者：
Hemani G;Bowden J;Davey Smith G
通讯作者：
Davey Smith G
影响因子：
9.8
作者：
Ameur, Adam;Enroth, Stefan;Gyllensten, Ulf
通讯作者：
Gyllensten, Ulf