Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia
- Authors: Olmastroni, Elena; Gazzotti, Marta; Averna, Maurizio; Arca, Marcello; Tarugi, Patrizia; Calandra, Sebastiano; Bertolini, Stefano; Catapano, Alberico L; Casula, Manuela; Laura D'Erasmo, Angelo Baldassare Cefalu, Andrea Bartuli, Paola Sabrina Buonuomo, Andrea Benso, Guglielmo Beccuti, Giacomo Biasucci, Maria Elena Capra, Gianni Biolo, Pierandrea Vinci, Luca Bonanni, Claudio Borghi, Sergio D'Addato, Antonio Carlo Bossi, Giancarla Meregalli, Adriana Branchi, Paolo Calabrò, Francesca Carubbi, Fabio Nascimbeni, Francesco Cipollone, Marco Bucci, Nadia Citroni, Maria Del Ben, Francesco Baratta, Massimo Federici, Martina Montagna, Claudio Ferri, Serena Notargiacomo, Anna Maria Fiorenza, Emanuela Colombo, Giuliana Fortunato, Maria Donata Di Taranto, Andrea Giaccari, Simona Moffa, Francesco Giorgino, Sergio Di Molfetta, Ornella Guardamagna, Luisa De Sanctis, Arcangelo Iannuzzi, Raimondo Cavallaro, Gabriella Iannuzzo, Marco Gentile, Lorenzo Iughetti, Patrizia Bruzzi, Salvatore Lia, Alessandro Lupi, Giuseppe Mandraffino, Arianna Toscano, Rossella Marcucci, Martina Berteotti, Lorenzo Maroni, Fabiana Locatelli, Tiziana Montalcini, Giuliana Mombelli, Sandro Muntoni, Davide Baldera, Gianfranco Parati, Angelina Passaro, Valerio Pecchioli, Cristina Pederiva, Giuseppe Banderali, Antonio Pipolo, Debora D'Elia, Matteo Pirro, Vanessa Bianconi, Livia Pisciotta, Elena Formisano, Francesco Purrello, Roberto Scicali, Elena Repetti, Elena Cantino, Elisabetta Rinaldi, Elena Sani, Riccardo Sarzani, Francesco Spannella, Francesco Sbrana, Beatrice Dal Pino, Patrizia Suppressa, Veronica Cocco, Chiara Trenti, Emanuele Alberto Negri, Josè Pablo Werba, Alessandra Romandini, Sabina Zambon, Alberto Zambon, Maria Grazia Zenti, Giulia Fainelli, Fabio Pellegatta, Liliana Grigore, Katia Bonomo, Eleonora Capatti, Ada Cutolo, Fabio Fimiani, Simonetta Genovesi, Sandro Inchiostro, Chiara Pavanello, Roberta Pujia, Alon Schaffer
- Publication year: 2023
- Type: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/596973
Abstract
: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH.