The PLIN4 variant rs8887 modulates obesity related phenotypes in humans through creation of a novel miR-522 seed site.
The PLIN4 variant rs8887 modulates obesity related phenotypes in humans through creation of a novel miR-522 seed site.
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DOI：
10.1371/journal.pone.0017944
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发表时间：
2011-04-20
期刊：
影响因子：
3.7
通讯作者：
Ordovas JM
中科院分区：
文献类型：
--
作者：
Richardson K;Louie-Gao Q;Arnett DK;Parnell LD;Lai CQ;Davalos A;Fox CS;Demissie S;Cupples LA;Fernandez-Hernando C;Ordovas JM
PLIN 4是脂质储存液滴（LSD）蛋白的PAT家族的成员。使用荟萃分析研究了人PLIN 4处的七个单核苷酸多态性（SNP）与肥胖相关表型之间的关联，然后确定这些表型是否受PLIN 4 SNP和膳食PUFA之间的相互作用调节。样本由来自两个欧洲血统人群的受试者组成。我们证明了rs 8887与人体测量学的关联。荟萃分析表明rs 8887次要等位基因与PUFA n3调节人体测量学之间的显着相互作用。rs 884164显示与n3和n6 PUFA调节人体测量和脂质表型的相互作用。对围绕rs 8887小A等位基因的PLIN 4 3′UTR序列的计算机分析预测了人类microRNA-522（miR-522）的种子位点，表明了一种功能机制。我们的数据显示，与G等位基因相比，携带rs 8887的A等位基因的PLIN 4 3′UTR荧光素酶报告基因对miR-522模拟物的响应减少。这些结果表明，PLIN 4基因座的变异及其与PUFA的相互作用作为肥胖相关表型的调节剂，部分通过产生miR-522调控位点起作用。
PLIN4 is a member of the PAT family of lipid storage droplet (LSD) proteins. Associations between seven single nucleotide polymorphisms (SNPs) at human PLIN4 with obesity related phenotypes were investigated using meta-analysis followed by a determination if these phenotypes are modulated by interactions between PLIN4 SNPs and dietary PUFA. Samples consisted of subjects from two populations of European ancestry. We demonstrated association of rs8887 with anthropometrics. Meta-analysis demonstrated significant interactions between the rs8887 minor allele with PUFA n3 modulating anthropometrics. rs884164 showed interaction with both n3 and n6 PUFA modulating anthropometric and lipid phenotypes. In silico analysis of the PLIN4 3′UTR sequence surrounding the rs8887 minor A allele predicted a seed site for the human microRNA-522 (miR-522), suggesting a functional mechanism. Our data showed that a PLIN4 3′UTR luciferase reporter carrying the A allele of rs8887 was reduced in response to miR-522 mimics compared to the G allele. These results suggest variation at the PLIN4 locus, and its interaction with PUFA as a modulator of obesity related phenotypes, acts in part through creation of a miR-522 regulatory site.