APOA5 and triglyceride metabolism, lesson from human APOA5 deficiency.
OBJECTIVE
In this review we compare the phenotype and lipoprotein abnormalities of some patients who were found to carry mutations in the APOA5 gene predicted to result in apolipoprotein A-V deficiency.


RESULTS
The sequencing of the APOA5 gene in patients with primary hypertriglyceridemia, in whom mutations of the LPL and APOC2 genes had been excluded, led to the identification of four families with two different mutations in this gene predicted to result in truncated apolipoprotein A-V. The first mutation (Q148X) was found in a homozygous state in a child with severe type V hyperlipidemia, some clinical manifestations of chylomicronemia syndrome and a slight reduction in plasma postheparin lipoprotein lipase activity. Carriers of a different mutation (Q139X) were recently reported. Four Q139X heterozygotes had type V hyperlipidemia and markedly reduced plasma postheparin lipoprotein lipase activity. The hypertriglyceridemic Q139X heterozygote had other factors that could have contributed to hypertriglyceridemia. ApoB-100 kinetic studies in hypertriglyceridemic Q139X heterozygotes revealed an impairment of very low-density lipoprotein catabolism.


CONCLUSIONS
Mutations in the APOA5 gene, leading to truncated apolipoprotein A-V devoid of lipid-binding domains located in the carboxy-terminal end of the protein, if present in the homozygous state, are expected to cause severe type V hyperlipidemia in patients with no mutations in LPL or APOC2 genes. If present in the heterozygous state, these mutations predispose to hypertriglyceridemia in combination with other genetic factors or pathological conditions.
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy. sebcal@unimo.it
Sebastiano
S
Calandra
Claudio
C
Priore Oliva
Patrizia
P
Tarugi
Stefano
S
Bertolini
D000818:Animals; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D014280:Triglycerides; D008071:Lipoprotein Lipase