Claudio Rabacchi1, Livia Pisciotta2, Angelo B Cefalù3, Davide Noto3, Raffaele Fresa2, Patrizia Tarugi1, Maurizio Averna3, Stefano Bertolini4, Sebastiano Calandra5. 1. Department of Life Sciences, University of Modena and Reggio Emilia, Italy. 2. Department of Internal Medicine, University of Genova, Italy. 3. Department of Internal Medicine and Medical Specialities, University of Palermo, Italy. 4. Department of Internal Medicine, University of Genova, Italy. Electronic address: stefbert@unige.it. 5. Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Italy. Electronic address: sebcal@unimore.it.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Suzanne A Al-Bustan; Ahmad Al-Serri; Babitha G Annice; Majed A Alnaqeeb; Wafa Y Al-Kandari; Mohammed Dashti Journal: PLoS One Date: 2018-02-13 Impact factor: 3.240
Authors: Louis St L O'Dea; James MacDougall; Veronica J Alexander; Andres Digenio; Brant Hubbard; Marcello Arca; Patrick M Moriarty; John J P Kastelein; Eric Bruckert; Handrean Soran; Joseph L Witztum; Robert A Hegele; Daniel Gaudet Journal: J Endocr Soc Date: 2019-10-11
Authors: Chan Joo Lee; Chi Yoon Oum; Yunbeom Lee; Sungha Park; Seok Min Kang; Donghoon Choi; Yangsoo Jang; Ji Hyun Lee; Sang Hak Lee Journal: Yonsei Med J Date: 2018-01 Impact factor: 2.759