Variants in the apolipoprotein A5 (APOA5) gene are associated with lipids levels, mainly HDL cholesterol, and with related dysfunctions including the metabolic syndrome. Several of these variants map in UTRs, such as the SNP rs651821 localized in the 5′UTR region.101 By searching this SNP in a recently published catalog of gene expression data (https://www.gtexportal.org/home/),102 we observed that it is an eQTL (in the adipose – subcutaneous specific tissue) for a long non coding RNA gene (RP11-109L13.1) located 400 kb downstream the APOA5 gene. The effective implication of this gene in lipid modulation is suggested by a second variant mapping in the 3′UTR of the gene and showing pleiotropic effects on triglycerides and HDL-C levels: the SNP rs2266788.103 Interestingly, in a more recent work, Caussy and colleagues showed that the less frequent allele of rs2266788, belonging to APOA5 haplotype 2 (APOA5*2), reduces APOA5 expression at the post-transcriptional level by creating a functional target site for miRNA485-5p, mainly expressed in the liver. Therefore, the increased level of triglycerides in the presence of APOA5*2 could be caused by the APOA5 downregulation mediated by miRNA485-5p.104
