Maria Donata Di Taranto1, Antonino Staiano2, Maria Nicoletta D'Agostino3, Antonietta D'Angelo3, Elena Bloise4, Alberto Morgante4, Gennaro Marotta5, Marco Gentile5, Paolo Rubba5, Giuliana Fortunato6. 1. IRCCS SDN, Via Emanuele Gianturco 113, 80143 Napoli, Italy. 2. Dipartimento di Scienze e Tecnologie, Università di Napoli Parthenope, Isola C4, Centro Direzionale, 80143 Napoli, Italy. 3. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131 Napoli, Italy; CEINGE Biotecnologie Avanzate S.C. a r.l., Via Gaetano Salvatore 486, 80145 Napoli, Italy. 4. CEINGE Biotecnologie Avanzate S.C. a r.l., Via Gaetano Salvatore 486, 80145 Napoli, Italy. 5. Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131 Napoli, Italy. 6. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131 Napoli, Italy; CEINGE Biotecnologie Avanzate S.C. a r.l., Via Gaetano Salvatore 486, 80145 Napoli, Italy. Electronic address: fortunat@unina.it.
Abstract
BACKGROUND: Familial combined hyperlipidemia (FCH) is a polygenic and multifactorial disease characterized by a variable phenotype showing increased levels of triglycerides and/or cholesterol. The aim of this study was to identify single nucleotides (SNPs) in lipid-related genes associated with FCH. METHODS AND RESULTS: Twenty SNPs in lipid-related genes were studied in 142 control subjects and 165 FCH patients after excluding patients with mutations in the LDLR gene and patients with the E2/E2 genotype of APOE. In particular, we studied the 9996G > A (rs2073658) and 11235C > T (rs3737787) variants in the Upstream Stimulatory Factor 1 gene (USF1), and the -1131T > C (rs662799) and S19W (rs3135506) variants in the Apolipoprotein A-V gene (APOA5). We found that the frequencies of these variants differed between patients and controls and that are associated with different lipid profiles. At multivariate logistic regression SNP S19W in APOA5 remained significantly associated with FCH independently of age, sex, BMI, cholesterol and triglycerides. CONCLUSIONS: Our results show that the USF1 and APOA5 polymorphisms are associated with FCH and that the S19W SNP in the APOA5 gene is associated to the disease independently of total cholesterol, triglycerides and BMI. However, more extensive studies including other SNPs such as rs2516839 in USF1, are required.
BACKGROUND: Familial combined hyperlipidemia (FCH) is a polygenic and multifactorial disease characterized by a variable phenotype showing increased levels of triglycerides and/or cholesterol. The aim of this study was to identify single nucleotides (SNPs) in lipid-related genes associated with FCH. METHODS AND RESULTS: Twenty SNPs in lipid-related genes were studied in 142 control subjects and 165 FCH patients after excluding patients with mutations in the LDLR gene and patients with the E2/E2 genotype of APOE. In particular, we studied the 9996G > A (rs2073658) and 11235C > T (rs3737787) variants in the Upstream Stimulatory Factor 1 gene (USF1), and the -1131T > C (rs662799) and S19W (rs3135506) variants in the Apolipoprotein A-V gene (APOA5). We found that the frequencies of these variants differed between patients and controls and that are associated with different lipid profiles. At multivariate logistic regression SNP S19W in APOA5 remained significantly associated with FCH independently of age, sex, BMI, cholesterol and triglycerides. CONCLUSIONS: Our results show that the USF1 and APOA5 polymorphisms are associated with FCH and that the S19W SNP in the APOA5 gene is associated to the disease independently of total cholesterol, triglycerides and BMI. However, more extensive studies including other SNPs such as rs2516839 in USF1, are required.