Background. Angiopoietin-like 3 (ANGPTL3) regulates lipoproteinmetabolism by modulating extracellular lipases. Loss-offunction mutations in ANGPTL3 gene cause familial combinedhypolipidemia (FHBL2). The mode of inheritance and hepaticand vascular consequences of FHBL2 have not been fully elucidated.To get further insights on these aspects, we re-evaluated theclinical and the biochemical characteristics of all reported casesof FHBL2.Methods and Results. One hundred fteen FHBL2 individualscarrying 13 different mutations in the ANGPTL3 gene (14 homozygotes,8 compound heterozygotes and 93 heterozygotes) and 402controls were considered. Carriers of 2 mutant alleles had undetectableplasma levels of ANGPTL3 protein whereas heterozygotesshowed a reduction ranging from 34% to 88%, according to genotype.Compared to controls, homozygotes as well as heterozygotesshowed a signi cant reduction of all plasma lipoproteins, while nodifference in Lp(a) levels was detected between groups. The prevalenceof fatty liver was not different in FHBL2 subjects comparedto controls. Notably diabetes mellitus and cardiovascular diseasewere absent among homozygotes.Conclusions. FHBL2 trait is inherited in a co-dominant mannerand the lipid-lowering effect of 2 ANGPTL3 mutant alleleswas more than 4 times larger than that of one mutant allele. Nochanges in Lp(a) were detected in FHBL2. Furthermore, ouranalysis con rmed that FHBL2 is not associated with adverseclinical sequelae. The possibility that FHBL2 confers lower riskof diabetes and cardiovascular disease warrant more detailedinvestigations.
|Number of pages||10|
|Publication status||Published - 2013|
- Cell Biology