Supplementary Material for: A CpG-SNP Located within the <b><i>ARPC3</i></b> Gene Promoter Is Associated with Hypertriglyceridemia in Severely Obese Patients

<b><i>Aims:</i></b> 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 (<i>ARPC3</i>), a gene recently linked to adipogenesis and lipid accumulation, with metabolic syndrome (MetS) features in severely obese patients. <b><i>Methods:</i></b> Prioritized SNPs within the <i>ARPC3</i> 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. <b><i>Results:</i></b> 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<sup>-2</sup>), 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 <i>ARPC3</i> promoter-associated CpG site cg10738648 in both visceral adipose tissue and blood. <i>ARPC3</i> expression levels showed a strong correlation with plasma TG levels (r = 0.70; p = 0.02). <b><i>Conclusions:</i></b> 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.