The PLIN4 Variant rs8887 Modulates Obesity Related Phenotypes in Humans through Creation of a Novel miR-522 Seed Site
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.
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The PLIN4 Variant rs8887 Modulates Obesity Related
Phenotypes in Humans through Creation of a Novel miR-522 Seed
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