An APOA5 3′ UTR Variant Associated with Plasma Triglycerides Triggers APOA5 Downregulation by Creating a Functional miR-485-5p Binding Site

APOA5 c.∗158C>T (rs2266788), located in the 3′ UTR, belongs to APOA5 haplotype 2 (APOA5∗2), which is strongly associated with plasma triglyceride levels and modulates the occurrence of both moderate and severe hypertriglyceridemia. Individuals with APOA5∗2 display reduced APOA5 expression at the posttranscriptional level. However, the functionality of this haplotype remains unclear. We hypothesized that the hypertriglyceridemic effects of APOA5∗2 could involve miRNA regulation in the APOA5 3′ UTR. Bioinformatic studies have identified the creation of a potential miRNA binding site for liver-expressed miR-485-5p (MIRN485-5p) in the mutant APOA5 3′ UTR with the c.∗158C allele. In human embryonic kidney 293T (HEK293T) cells cotransfected with an APOA5 3′ UTR luciferase reporter vector and a miR485-5p precursor, c.∗158C allele expression was significantly decreased. Moreover, in HuH-7 cells endogenously expressing miR-485-5p, we observed that luciferase activity was significantly lower in the presence of the c.∗158C allele than in the presence of the c.∗158T allele, which was completely reversed by a miR-485-5p inhibitor. We demonstrated that the rare c.∗158C APOA5 allele creates a functional target site for liver-expressed miR-485-5p. Therefore, we propose that the well-documented hypertriglyceridemic effect of APOA5∗2 involves an APOA5 posttranscriptional downregulation mediated by miR-485-5p

Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers

Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD), are rare genetic diseases that cause malnutrition, failure to thrive, growth failure and vitamin E deficiency, as well as other complications. Recently, the gene implicated in CRD was identified. The diagnosis is often delayed because symptoms are nonspecific. Treatment and follow-up remain poorly defined

Mise au point d'une technique de mesure de l'activité des récepteurs LDL par cytométrie en flux

LYON1-BU Santé (693882101) / SudocSudocFranceF

Recherche de mutations sur la protéine ABCA1 chez des patients atteints d'hypoHDLémie familiale profonde

LYON1-BU Santé (693882101) / SudocSudocFranceF

Le gène de l'apolipoprotéine E (détection des mutations et détermination des polymorphismes par dHPLC (denaturing High-Performance Liquid Chromatopraphy))

LYON1-BU Santé (693882101) / SudocSudocFranceF

Mise au point d'une méthode de séparation des chylomicrons de serums hypertriglycéridémiques par technique FPLC

LYON1-BU Santé (693882101) / SudocSudocFranceF

Les mutations du gène du trypsinogène dans les pancréatites (application à des patients hypertriglycéridémiques)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Pancréatites chez des patients hypertriglycéridémiques (implication du trypsinogène)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Pancréatites chez des patients hypertriglycéridémiques (implication du gène SPINK1)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Maladie de rétention des chylomicrons (maladie d'Anderson) (impact clinique et moléculaire de trois nouvelles mutations)

LYON1-BU Santé (693882101) / SudocSudocFranceF