AIMS: To test the potential association of cytosine-phosphate-guanine dinucleotides (CpG)-single-nucleotide polymorphisms (SNPs) located within actin-related protein 2/3 complex subunit 3 (ARPC3), a gene recently linked to adipogenesis and lipid accumulation, with metabolic syndrome (MetS) features in severely obese patients. METHODS: Prioritized SNPs within the ARPC3 locus were genotyped and tested for associations with MetS features in a cohort of 1,749 obese patients with and without MetS. Association testing with CpG methylation levels was performed in a methylation sub-cohort of 16 obese men. RESULTS: A significant association was found between the CpG-SNP rs3759384 (C>T) and plasma triglyceride (TG) levels (false discovery rate-corrected p = 3.5 × 10-2), with 0.6% of the phenotypic variance explained by the CpG-SNP, and with TT homozygotes showing the highest plasma TG levels (1.89 mmol/l). The carriers of the rs3759384 T allele also showed a significant decrease in methylation levels of the ARPC3 promoter-associated CpG site cg10738648 in both visceral adipose tissue and blood. ARPC3 expression levels showed a strong correlation with plasma TG levels (r = 0.70; p = 0.02). CONCLUSIONS: The increased plasma TG levels found in homozygous rs3759384 T allele carriers argue for a relevant role of this CpG-SNP in lipid management among obese individuals, which may be driven by an epigenetic-mediated mechanism.
AIMS: To test the potential association of cytosine-phosphate-guanine dinucleotides (CpG)-single-nucleotide polymorphisms (SNPs) located within actin-related protein 2/3 complex subunit 3 (ARPC3), a gene recently linked to adipogenesis and lipid accumulation, with metabolic syndrome (MetS) features in severely obesepatients. METHODS: Prioritized SNPs within the ARPC3 locus were genotyped and tested for associations with MetS features in a cohort of 1,749 obesepatients with and without MetS. Association testing with CpG methylation levels was performed in a methylation sub-cohort of 16 obesemen. RESULTS: A significant association was found between the CpG-SNP rs3759384 (C>T) and plasma triglyceride (TG) levels (false discovery rate-corrected p = 3.5 × 10-2), with 0.6% of the phenotypic variance explained by the CpG-SNP, and with TT homozygotes showing the highest plasma TG levels (1.89 mmol/l). The carriers of the rs3759384 T allele also showed a significant decrease in methylation levels of the ARPC3 promoter-associated CpG site cg10738648 in both visceral adipose tissue and blood. ARPC3 expression levels showed a strong correlation with plasma TG levels (r = 0.70; p = 0.02). CONCLUSIONS: The increased plasma TG levels found in homozygous rs3759384 T allele carriers argue for a relevant role of this CpG-SNP in lipid management among obese individuals, which may be driven by an epigenetic-mediated mechanism.
Authors: Augusto Anguita-Ruiz; Mireia Bustos-Aibar; Julio Plaza-Díaz; Andrea Mendez-Gutierrez; Jesús Alcalá-Fdez; Concepción María Aguilera; Francisco Javier Ruiz-Ojeda Journal: Int J Mol Sci Date: 2021-03-09 Impact factor: 5.923