The plin4 variant rs8887 modulates obesity related phenotypes in humans through creation of a novel mir-522 seed site

Kris Richardson; Qiong Louie-Gao; Donna K. Arnett; Laurence D. Parnell; Chao Qiang Lai; Alberto Davalos; Caroline S. Fox; Serkalem Demissie; L. Adrienne Cupples; Carlos Fernandez-Hernando; Jose M. Ordovas

doi:10.1371/journal.pone.0017944

The plin4 variant rs8887 modulates obesity related phenotypes in humans through creation of a novel mir-522 seed site

Kris Richardson, Qiong Louie-Gao, Donna K. Arnett, Laurence D. Parnell, Chao Qiang Lai, Alberto Davalos, Caroline S. Fox, Serkalem Demissie, L. Adrienne Cupples, Carlos Fernandez-Hernando, Jose M. Ordovas

College of Public Health

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

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.

Original language	English
Article number	e17944
Journal	PLoS ONE
Volume	6
Issue number	4
DOIs	https://doi.org/10.1371/journal.pone.0017944
State	Published - 2011

Bibliographical note

Funding Information:
Study protocol approval was obtained from the Human Studies Committee of Institutional Review Board at the University of Minnesota, University of Utah, and Tufts Medical Center. All participants provided written informed consent. The detailed methodology and design of the GOLDN study has been described previously , . Briefly, GOLDN is part of the Program for the Genetic Interactions Network and is funded by the NIH. Participants were recruited from pedigrees from two genetically homogenous National Heart, Lung, and Blood Institute Family Heart Study field centers in Minnesota and Utah, both predominately white populations. There were 1086 subjects with complete phenotype, dietary and genotype data. Dietary intake was estimated by use of the Dietary Health Questionnaire (DHQ) which consists of 124 food items and includes both portion size and dietary supplement questions .

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Richardson, K., Louie-Gao, Q., Arnett, D. K., Parnell, L. D., Lai, C. Q., Davalos, A., Fox, C. S., Demissie, S., Cupples, L. A., Fernandez-Hernando, C., & Ordovas, J. M. (2011). The plin4 variant rs8887 modulates obesity related phenotypes in humans through creation of a novel mir-522 seed site. PLoS ONE, 6(4), Article e17944. https://doi.org/10.1371/journal.pone.0017944

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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.",

author = "Kris Richardson and Qiong Louie-Gao and Arnett, {Donna K.} and Parnell, {Laurence D.} and Lai, {Chao Qiang} and Alberto Davalos and Fox, {Caroline S.} and Serkalem Demissie and Cupples, {L. Adrienne} and Carlos Fernandez-Hernando and Ordovas, {Jose M.}",

note = "Funding Information: Study protocol approval was obtained from the Human Studies Committee of Institutional Review Board at the University of Minnesota, University of Utah, and Tufts Medical Center. All participants provided written informed consent. The detailed methodology and design of the GOLDN study has been described previously , . Briefly, GOLDN is part of the Program for the Genetic Interactions Network and is funded by the NIH. Participants were recruited from pedigrees from two genetically homogenous National Heart, Lung, and Blood Institute Family Heart Study field centers in Minnesota and Utah, both predominately white populations. There were 1086 subjects with complete phenotype, dietary and genotype data. Dietary intake was estimated by use of the Dietary Health Questionnaire (DHQ) which consists of 124 food items and includes both portion size and dietary supplement questions . ",

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AU - Lai, Chao Qiang

AU - Davalos, Alberto

AU - Fox, Caroline S.

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AU - Cupples, L. Adrienne

AU - Fernandez-Hernando, Carlos

AU - Ordovas, Jose M.

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AB - 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 site

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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