scholarly journals Screening of Peroxisome Proliferator-activated Receptors (PPARs) α, γ and δ Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-ethnic Malaysian Population

2015 ◽  
Vol 25 (4) ◽  
pp. 383 ◽  
Author(s):  
Phee-Phee Chia ◽  
Sook-Ha Fan ◽  
Yee-How Say
Keyword(s):  
Metabolic Syndrome ◽  
Demographic Data ◽  
Plasma Lipid ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Ethnic Population ◽  
Single Nucleotide ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ethnic Chinese ◽  
Peroxisome Proliferator Activated Receptors

<p class="Pa7"><strong>Objective: </strong>This study aimed to investigate the association of peroxisome proliferator-activated receptor (PPAR) genes <em>PPAR</em>α L162V, <em>PPAR</em><em>γ</em><em>2 </em>C161T and <em>PPAR</em><em>δ </em>T294C single nucleotide polymorphisms (SNPs) with obesity and metabolic syndrome (Met- S) in a multi-ethnic population in Kampar, Malaysia.</p><p class="Pa7"><strong>Methods: </strong>Socio-demographic data, anthropometric and biochemical measure­ments (plasma lipid profile, adiponectin and interleukin-6 [IL-6] levels) were taken from 307 participants (124 males; 180 obese; 249 Met-S; 97 Malays, 85 ethnic Chinese, 55 ethnic Indians).</p><p class="Pa7"><strong>Results: </strong>The overall minor allele frequen­cies were .08, .22 and .30 for <em>PPAR </em>α L162V, γ C161T, δ T294C, respectively. All SNPs were not associated with obesity, Met-S and obesity with/without Met-S by χ2 analysis, ethnicity-stratified and logistic re­gression analyses. Nevertheless, participants with V162 allele of <em>PPAR</em><em>α </em>had significantly higher IL-6, while those with T161 allele of <em>PPAR</em><em>γ</em><em>2 </em>had significantly lower HOMA-IR.</p><p><strong>Conclusions: </strong>All <em>PPAR </em>SNPs were not associated with obesity and Met-S in the suburban population of Kampar, Malay­sia, where only <em>PPAR</em><em>α </em>V162 and <em>PPAR</em><em>γ</em><em>2 </em>T161 alleles were associated with plasma IL-6 and HOMA-IR, respectively. <em>Ethn Dis. </em>2015;25(4):383-390; doi:10.18865/ ed.25.4.383</p>

scholarly journals ILRUN , a Human Plasma Lipid GWAS Locus, Regulates Lipoprotein Metabolism in Mice

2020 ◽  
Vol 127 (11) ◽  
pp. 1347-1361 ◽  
Author(s):  
Xin Bi ◽  
Takashi Kuwano ◽  
Paul C. Lee ◽  
John S. Millar ◽  
Li Li ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver Transcriptome ◽  
Artery Disease

Rationale: Single-nucleotide polymorphisms near the ILRUN (inflammation and lipid regulator with ubiquitin-associated–like and NBR1 [next to BRCA1 gene 1 protein]-like domains) gene are genome-wide significantly associated with plasma lipid traits and coronary artery disease (CAD), but the biological basis of this association is unknown. Objective: To investigate the role of ILRUN in plasma lipid and lipoprotein metabolism. Methods and Results: ILRUN encodes a protein that contains a ubiquitin-associated–like domain, suggesting that it may interact with ubiquitinylated proteins. We generated mice globally deficient for Ilrun and found they had significantly lower plasma cholesterol levels resulting from reduced liver lipoprotein production. Liver transcriptome analysis uncovered altered transcription of genes downstream of lipid-related transcription factors, particularly PPARα (peroxisome proliferator-activated receptor alpha), and livers from Ilrun -deficient mice had increased PPARα protein. Human ILRUN was shown to bind to ubiquitinylated proteins including PPARα, and the ubiquitin-associated–like domain of ILRUN was found to be required for its interaction with PPARα. Conclusions: These findings establish ILRUN as a novel regulator of lipid metabolism that promotes hepatic lipoprotein production. Our results also provide functional evidence that ILRUN may be the casual gene underlying the observed genetic associations with plasma lipids at 6p21 in human.

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