RESUMO
BACKGROUND AND AIMS: Type I hyperlipoproteinemia, also known as familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disorder caused by variants in LPL, APOC2, APOA5, LMF1 or GPIHBP1 genes. The aim of this study was to identify novel variants in the LPL gene causing lipoprotein lipase deficiency and to understand the molecular mechanisms. METHODS AND RESULTS: A total of 3 individuals with severe hypertriglyceridemia and recurrent pancreatitis were selected from the Lipid Clinic at Sahlgrenska University Hospital and LPL was sequenced. In vitro experiments were performed in human embryonic kidney 293T/17 (HEK293T/17) cells transiently transfected with wild type or mutant LPL plasmids. Cell lysates and media were used to analyze LPL synthesis and secretion. Media were used to measure LPL activity. Patient 1 was compound heterozygous for three known variants: c.337T > C (W113R), c.644G > A (G215E) and c.1211T > G (M404R); patient 2 was heterozygous for the known variant c.658A > C (S220R) while patient 3 was homozygous for a novel variant in the exon 5 c.679G > T (V227F). All the LPL variants identified were loss-of-function variants and resulted in a substantial reduction in the secretion of LPL protein. CONCLUSION: We characterized at the molecular level three known and one novel LPL variants causing type I hyperlipoproteinemia showing that all these variants are pathogenic.
Assuntos
Hiperlipoproteinemia Tipo I/genética , Lipase Lipoproteica/genética , Mutação , Adulto , Idoso , Feminino , Predisposição Genética para Doença , Células HEK293 , Heterozigoto , Homozigoto , Humanos , Hiperlipoproteinemia Tipo I/sangue , Hiperlipoproteinemia Tipo I/diagnóstico , Hiperlipoproteinemia Tipo I/enzimologia , Hipertrigliceridemia/sangue , Hipertrigliceridemia/enzimologia , Hipertrigliceridemia/genética , Lipídeos/sangue , Lipase Lipoproteica/metabolismo , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Pancreatite/enzimologia , Pancreatite/genética , Fenótipo , Recidiva , TransfecçãoRESUMO
The World elderly population is expected to double before 2050. Unhealthy habits and unhealthy lifestyles are commonly associated with age-related diseases or their worsening. Modification in daily lifestyle and diet may help preventing age-related diseases onset and efficiently affecting their evolution, thus promoting the Healthy Aging process, concept recently coined to describe the disease-free aging process. This review highlights the role of nutrition science in promoting healthy aging. Since the Mediterranean Model demonstrated to be a useful style in supporting healthy aging, promotion of this correct lifestyle by health policies seems to be the best approach to achieve this target.