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<p>Apolipoprotein A2 is the second most abundant protein in high-density lipoproteins and plays an important role in lipid and glucose metabolism. <i>APOA2</i> has been identified as a candidate gene influencing fat-related traits in pigs, and genetic variation has been associated with its hepatic expression. The aim of this study was to identify regulatory polymorphisms in the <i>APOA2</i> promoter and assess their impact on gene expression. A total of 441 pigs from three backcross populations were analyzed. Four polymorphisms were identified in the <i>APOA2</i> promoter, and a genome-wide association study identified rs339777757 as the most significant variant associated with <i>APOA2</i> expression in liver. This variant is located at a predicted binding site of RORα, a nuclear receptor regulating apolipoprotein expression. RORα cotransfection with <i>APOA2</i> promoter-driven luciferase constructs in HepG2 cells showed higher promoter activity of the rs339777757 C allele compared to the T allele. Our findings demonstrate that rs339777757 is a functional regulatory variant modulating <i>APOA2</i> expression in the liver and support a functional role for RORα in this transcriptional regulatory mechanism. Since <i>APOA2</i> plays a key role in lipid metabolism, this variant is likely to contribute to phenotypic variability in fat composition and meat quality traits, representing a potential target for improving pork quality. Additionally, these findings support the relevance of pigs as a model for studying metabolic regulation with potential implications for human health.</p>

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A functional variant in the porcine APOA2 promoter alters hepatic gene expression via RORα

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月30日

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  • Junhui Liu,
  • Carles Hernández-Banqué,
  • Olga González-Rodríguez,
  • Anna Castelló,
  • Lourdes Criado-Mesas,
  • Miao Zhang,
  • Alba Chofre,
  • Bart Staels,
  • Josep M. Folch,
  • Maria Ballester

摘要

Apolipoprotein A2 is the second most abundant protein in high-density lipoproteins and plays an important role in lipid and glucose metabolism. APOA2 has been identified as a candidate gene influencing fat-related traits in pigs, and genetic variation has been associated with its hepatic expression. The aim of this study was to identify regulatory polymorphisms in the APOA2 promoter and assess their impact on gene expression. A total of 441 pigs from three backcross populations were analyzed. Four polymorphisms were identified in the APOA2 promoter, and a genome-wide association study identified rs339777757 as the most significant variant associated with APOA2 expression in liver. This variant is located at a predicted binding site of RORα, a nuclear receptor regulating apolipoprotein expression. RORα cotransfection with APOA2 promoter-driven luciferase constructs in HepG2 cells showed higher promoter activity of the rs339777757 C allele compared to the T allele. Our findings demonstrate that rs339777757 is a functional regulatory variant modulating APOA2 expression in the liver and support a functional role for RORα in this transcriptional regulatory mechanism. Since APOA2 plays a key role in lipid metabolism, this variant is likely to contribute to phenotypic variability in fat composition and meat quality traits, representing a potential target for improving pork quality. Additionally, these findings support the relevance of pigs as a model for studying metabolic regulation with potential implications for human health.