The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter.
The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter.
复制标题
DOI：
10.1002/mnfr.201500436
复制
发表时间：
2016-02
影响因子：
5.2
通讯作者：
Arnett DK
中科院分区：
文献类型：
--
作者：
Ma Y;Smith CE;Lai CQ;Irvin MR;Parnell LD;Lee YC;Pham LD;Aslibekyan S;Claas SA;Tsai MY;Borecki IB;Kabagambe EK;Ordovás JM;Absher DM;Arnett DK
Omega-3 PUFAs（n-3 PUFAs）可降低IL-6基因表达，但其对转录调控机制的影响尚不清楚。我们的目的是进行综合分析与人口和体外研究，系统地探讨n-3多不饱和脂肪酸，DNA甲基化，单核苷酸多态性（SNP），基因表达和IL 6的蛋白浓度之间的关系。使用降脂药物和饮食网络遗传学（GOLDN）研究和DNA元件百科全书（ENCODE）联盟的数据，我们发现IL 6启动子cg 01770232的高甲基化与较高的IL-6血浆浓度（p = 0.03）和较高的IL-6基因表达（p = 0.0005）相关。较高的循环总n-3 PUFA与较低的cg 01770232甲基化（p = 0.007）和较低的IL-6浓度（p = 0.02）相关。此外，IL 6 rs 2961298的等位基因与较高的cg 01770232甲基化相关（p = 2.55 × 10 - 7）。n-3 PUFA和cg 01770232甲基化之间的关联依赖于rs 2961298基因型（p = 0.02），但杂合子中较高的总n-3 PUFA与较低的cg 01770232甲基化相关（p = 0.04），而纯合子中则不相关。较高的n-3 PUFA与IL 6启动子较低的甲基化相关，其可能被IL 6 SNP修饰。
Omega-3 PUFAs (n-3 PUFAs) reduce IL-6 gene expression, but their effects on transcription regulatory mechanisms are unknown. We aimed to conduct an integrated analysis with both population and in vitro studies to systematically explore the relationships among n-3 PUFA, DNA methylation, single nucleotide polymorphisms (SNPs), gene expression, and protein concentration of IL6. Using data in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study and the Encyclopedia of DNA Elements (ENCODE) consortium, we found that higher methylation of IL6 promoter cg01770232 was associated with higher IL-6 plasma concentration (p = 0.03) and greater IL6 gene expression (p = 0.0005). Higher circulating total n-3 PUFA was associated with lower cg01770232 methylation (p = 0.007) and lower IL-6 concentration (p = 0.02). Moreover, an allele of IL6 rs2961298 was associated with higher cg01770232 methylation (p = 2.55 × 10−7). The association between n-3 PUFA and cg01770232 methylation was dependent on rs2961298 genotype (p = 0.02), but higher total n-3 PUFA was associated with lower cg01770232 methylation in the heterozygotes (p = 0.04) not in the homozygotes. Higher n-3 PUFA is associated with lower methylation at IL6 promoter, which may be modified by IL6 SNPs.