title: The PLIN4 variant rs8887 modulates obesity related phenotypes in humans through creation of a novel miR-522 seed site.
abstract: 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.
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America. Kris.richardson@tufts.edu
authors.forename: Kris
authors.initials: K
authors.lastname: Richardson
authors.forename: Qiong
authors.initials: Q
authors.lastname: Louie-Gao
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.forename: Alberto
authors.initials: A
authors.lastname: Davalos
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Serkalem
authors.initials: S
authors.lastname: Demissie
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Hernando
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000483:Alleles; D000886:Anthropometry; D002352:Carrier Proteins; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D005260:Female; D040961:Genetic Drift; D006801:Humans; D050152:Intra-Abdominal Fat; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D000071229:Perilipin-4; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D050151:Subcutaneous Fat
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D004042:Dietary Fats, Unsaturated; C560599:MIRN522 microRNA, human; D035683:MicroRNAs; C560544:PLIN4 protein, human; D000071229:Perilipin-4; D010750:Phosphoproteins