The Functional SNPs in the 5' Regulatory Region of the Porcine PPARD Gene Have Significant Association with Fat Deposition Traits.

Yunxia Zhang,Zijun Zhang,Tengsen Gao,Yuanzhu Xiong,Guoshui Wang,Bo Zuo,Zaiyan Xu,Huimin Mao,Bin Lin,Yuanliang Mao,Dechao Yan,Shanyao Hu,Litong Wang,Liangxue Lai

doi:10.1371/journal.pone.0143734

Abstract

Peroxisome proliferator-activated receptor delta (PPARD) is a key regulator of lipid metabolism, insulin sensitivity, cell proliferation and differentiation. In this study, we identified two Single Nucleotide Polymorphisms (SNPs, g.1015 A>G and g.1018 T>C) constituting four haplotypes (GT, GC, AC and AT) in the 5’ regulatory region of porcine PPARD gene. Functional analysis of the four haplotypes showed that the transcriptional activity of the PPARD promoter fragment carrying haplotype AC was significantly lower than that of the other haplotypes in 3T3-L1, C2C12 and PK-15 cells, and haplotype AC had the lowest binding capacities to the nuclear extracts. Transcription factor 7-like 2 (TCF7L2) enhanced the transcription activities of promoter fragments of PPARD gene carrying haplotypes GT, GC and AT in C2C12 and 3T3-L1 cells, and increased the protein expression of PPARD gene in C2C12 myoblasts. TCF7L2 differentially bound to the four haplotypes, and the binding capacity of TCF7L2 to haplotype AC was the lowest. There were significant associations between -655A/G and fat deposition traits in three pig populations including the Large White × Meishan F2 pigs, France and American Large White pigs. Pigs with genotype GG had significantly higher expression of PPARD at both mRNA and protein level than those with genotype AG. These results strongly suggested that the SNPs in 5’ regulatory region of PPARD genes had significant impact on pig fat deposition traits.

Highlights

Peroxisome proliferator-activated receptors (PPARs) are lipid-activated nuclear receptors belonging to the nuclear hormone receptor superfamily [1]
The results suggested that the allele A at rs80912557 of the Peroxisome proliferator-activated receptor delta (PPARD) was mostly linked with allele C at rs80964726, and allele G at rs80912557 was linked with allele T or C at rs80964726 in the pig population studied
Transcription factor 7-like 2 (TCF7L2) is a member of the T cell factor (TCF) family of transcription factors, and involved in the control of cell growth and signaling of winglesstype MMTV integration site family (Wnt) receptors [43]

Summary

Introduction

Peroxisome proliferator-activated receptors (PPARs) are lipid-activated nuclear receptors belonging to the nuclear hormone receptor superfamily [1]. The SNPs in PPARD Gene Have Association with Fat Deposition Traits. The funder provided support in the form of salaries for authors [ZZ, YM, HM, LW, GW], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Methods

Results

Conclusion