Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene expression.
Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene expression.
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DOI：
10.1371/journal.pone.0194610
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Chilton FH
中科院分区：
文献类型：
--
作者：
Reynolds LM;Howard TD;Ruczinski I;Kanchan K;Seeds MC;Mathias RA;Chilton FH
ω-6（n-6）和ω-3（n-3）长链（≥ 20个碳）多不饱和脂肪酸（LC-PUFA）在人类健康和疾病中起着关键作用。在诸如肝脏的组织中，来自膳食18碳PUFA的LC-PUFA的生物合成与脂肪酸去饱和酶（FADS）基因簇内的遗传变异高度相关，所述FADS基因簇包含编码LC-PUFA生物合成途径中的限速去饱和酶的FADS 1和FADS 2。然而，FADS遗传变异影响LC-PUFA生物合成的分子机制以及在哪些组织中尚不清楚。目前的研究检查了来自基因型-组织表达（GTEx）项目的44种不同人体组织（样本量范围为70-361）中FADS基因簇内常见单核苷酸多态性（SNP）与FADS 1和FADS 2基因表达之间的关联。FADS 1和FADS 2在所有44例组织中均表达。在FADS 1基因表达的12个组织和FADS 2基因表达的23个组织中鉴定了显著的顺式eQTL（每个基因的1兆碱基内，错误发现率，FDR<0.05，如GTEx所定义）。6个组织（包括动脉、食道、心脏、肌肉、神经和甲状腺）具有与FADS 1和FADS 2均显著相关的eQTL（FDR< 0.05）。有趣的是，所鉴定的eQTL一致地被发现与FADS 1和FADS 2表达的相反方向相关。总之，这项研究的结果表明，FADS基因簇内的常见SNP影响了许多组织中FADS 1和FADS 2的转录，并提出了关于这两种基因的反向表达如何影响中间分子（如LC-PUFA和含LC-PUFA的甘油酯水平）以及最终与炎症性疾病和大脑健康相关的临床表型的重要问题。
Omega-6 (n-6) and omega-3 (n-3) long (≥ 20 carbon) chain polyunsaturated fatty acids (LC-PUFAs) play a critical role in human health and disease. Biosynthesis of LC-PUFAs from dietary 18 carbon PUFAs in tissues such as the liver is highly associated with genetic variation within the fatty acid desaturase (FADS) gene cluster, containing FADS1 and FADS2 that encode the rate-limiting desaturation enzymes in the LC-PUFA biosynthesis pathway. However, the molecular mechanisms by which FADS genetic variants affect LC-PUFA biosynthesis, and in which tissues, are unclear. The current study examined associations between common single nucleotide polymorphisms (SNPs) within the FADS gene cluster and FADS1 and FADS2 gene expression in 44 different human tissues (sample sizes ranging 70–361) from the Genotype-Tissue Expression (GTEx) Project. FADS1 and FADS2 expression were detected in all 44 tissues. Significant cis-eQTLs (within 1 megabase of each gene, False Discovery Rate, FDR<0.05, as defined by GTEx) were identified in 12 tissues for FADS1 gene expression and 23 tissues for FADS2 gene expression. Six tissues had significant (FDR< 0.05) eQTLs associated with both FADS1 and FADS2 (including artery, esophagus, heart, muscle, nerve, and thyroid). Interestingly, the identified eQTLs were consistently found to be associated in opposite directions for FADS1 and FADS2 expression. Taken together, findings from this study suggest common SNPs within the FADS gene cluster impact the transcription of FADS1 and FADS2 in numerous tissues and raise important questions about how the inverse expression of these two genes impact intermediate molecular (such a LC-PUFA and LC-PUFA-containing glycerolipid levels) and ultimately clinical phenotypes associated with inflammatory diseases and brain health.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
DOI：
10.1051/rnd:19940603
发表时间：
1994-01-01
期刊：
REPRODUCTION NUTRITION DEVELOPMENT
影响因子：
--
作者：
BEZARD, J;BLOND, JP;CLOUET, P
通讯作者：
CLOUET, P
影响因子：
3.5
作者：
Dorajoo, Rajkumar;Sun, Ye;Friedlander, Yechiel
通讯作者：
Friedlander, Yechiel
影响因子：
16.6
作者：
Draisma, Harmen H. M.;Pool, Rene;Boomsma, Dorret I.
通讯作者：
Boomsma, Dorret I.