Your browser doesn't support javascript.
loading
Genetic variation in apolipoprotein A-V in hypertriglyceridemia.
Perera, Shehan D; Hegele, Robert A.
Affiliation
  • Perera SD; Departments of Biochemistry and Medicine, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street North, London, Ontario, Canada.
Curr Opin Lipidol ; 35(2): 66-77, 2024 04 01.
Article in En | MEDLINE | ID: mdl-38117614
ABSTRACT
PURPOSE OF REVIEW While biallelic rare APOA5 pathogenic loss-of-function (LOF) variants cause familial chylomicronemia syndrome, heterozygosity for such variants is associated with highly variable triglyceride phenotypes ranging from normal to severe hypertriglyceridemia, often in the same individual at different time points. Here we provide an updated overview of rare APOA5 variants in hypertriglyceridemia. RECENT

FINDINGS:

Currently, most variants in APOA5 that are considered to be pathogenic according to guidelines of the American College of Medical Genetics and Genomics are those resulting in premature termination codons. There are minimal high quality functional data on the impact of most rare APOA5 missense variants; many are considered as variants of unknown or uncertain significance. Furthermore, particular common polymorphisms of APOA5 , such as p.Ser19Trp and p.Gly185Cys in Caucasian and Asian populations, respectively, are statistically overrepresented in hypertriglyceridemia cohorts and are sometimes misattributed as being causal for chylomicronemia, when they are merely risk alleles for hypertriglyceridemia.

SUMMARY:

Both biallelic and monoallelic LOF variants in APOA5 are associated with severe hypertriglyceridemia, although the biochemical phenotype in the monoallelic state is highly variable and is often exacerbated by secondary factors. Currently, with few exceptions, the principal definitive mechanism for APOA5 pathogenicity is through premature truncation. The pathogenic mechanisms of most missense variants in APOA5 remain unclear and require additional functional experiments or family studies.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hypertriglyceridemia / Hyperlipoproteinemia Type I Limits: Humans Language: En Journal: Curr Opin Lipidol Journal subject: BIOQUIMICA Year: 2024 Document type: Article Affiliation country: Canadá

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hypertriglyceridemia / Hyperlipoproteinemia Type I Limits: Humans Language: En Journal: Curr Opin Lipidol Journal subject: BIOQUIMICA Year: 2024 Document type: Article Affiliation country: Canadá