Spectrum of mutations of the LPL gene identified in Italy in patients with severe hypertriglyceridemia

• Published in: Atherosclerosis Vol. 241; no. 1; pp. 79 - 86
• Main Authors: Rabacchi, Claudio, Pisciotta, Livia, Cefalù, Angelo B., Noto, Davide, Fresa, Raffaele, Tarugi, Patrizia, Averna, Maurizio, Bertolini, Stefano, Calandra, Sebastiano
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.07.2015
• Subjects: Adolescent; Adult; Aged; Biomarkers - blood; Cardiovascular; Child; Child, Preschool; DNA Mutational Analysis; Familial chylomicronemia; Female; Gene Frequency; Gene variants; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Hyperlipoproteinemia Type I - blood; Hyperlipoproteinemia Type I - diagnosis; Hyperlipoproteinemia Type I - enzymology; Hyperlipoproteinemia Type I - genetics; Infant; Italy; Lipoprotein lipase; Lipoprotein Lipase - genetics; Male; Middle Aged; Mutation; Pancreatitis; Pancreatitis - enzymology; Pancreatitis - genetics; Phenotype; Primary hypertriglyceridemia; Severity of Illness Index; Tertiary Care Centers; Triglycerides - blood; Young Adult; Italy; Familial chylomicronemia; Lipoprotein lipase; Primary hypertriglyceridemia; Gene variants; Pancreatitis
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2015.04.815

Monogenic hypertriglyceridemia (HTG) may result from mutations in some genes which impair the intravascular lipolysis of triglyceride (TG)-rich lipoproteins mediated by the enzyme Lipoprotein lipase (LPL). Mutations in the LPL gene are the most frequent cause of monogenic HTG (familial chylomicronemia) with recessive transmission. The LPL gene was resequenced in 149 patients with severe HTG (TG > 10 mmol/L) and 106 patients with moderate HTG (TG > 4.5 and <10 mmol/L) referred to tertiary Lipid Clinics in Italy. In the group of severe HTG, 26 patients (17.4%) were homozygotes, 9 patients (6%) were compound heterozygotes and 15 patients (10%) were simple heterozygotes for rare LPL gene variants. Single or multiple episodes of pancreatitis were recorded in 24 (48%) of these patients. There was no difference in plasma TG concentration between patients with or without a positive history of pancreatitis. Among moderate HTG patients, six patients (5.6%) were heterozygotes for rare LPL variants; two of them had suffered from pancreatitis. Overall 36 rare LPL variants were found, 15 of which not reported previously. Systematic analysis of close relatives of mutation carriers led to the identification of 44 simple heterozygotes (plasma TG 3.2 ± 4.1 mmol/L), none of whom had a positive history of pancreatitis. The prevalence of rare LPL variants in patients with severe or moderate HTG, referred to tertiary lipid clinics, was 50/149 (33.5%) and 6/106 (5.6%), respectively. Systematic analysis of relatives of mutation carriers is an efficient way to identify heterozygotes who may develop severe HTG. •The LPL gene was sequenced in individuals with severe/moderate hypertriglyceridemia.•Rare LPL variants were found in 33.5% of subjects with severe hypertriglyceridemia.•26 patients were homozygotes, 9 compound heterozygotes and 21 simple heterozygotes.•Thirty six rare LPL variants were identified, 15 of which not reported previously.•Screening of patients' relatives led to the identification of 44 simple heterozygotes.