title: Atherogenic dyslipidemia in children: evaluation of clinical, biochemical and genetic aspects.
abstract: The precursors of atherogenic dyslipidemia (AD) are not well defined. Therefore, we investigated 62 non-obese, non-diabetic AD and 221 normolipemic children. Anthropometric parameters, blood pressure and biochemical measures were obtained in index children, their parents and all available siblings. The heritability (h(2)) of anthropometric and biochemical traits was estimated by SOLAR. Rare and common variants in APOA1 and LPL genes were screened by re-sequencing. Compared to normolipemic, AD children showed increased body mass index, waist circumference, plasma glucose, insulin, ApoB, HOMA-IR, hs-CRP and lower adiponectin (p<0.001 for all). Metabolic syndrome was present in 40% of AD while absent in controls. All traits (except adiponectin and hs-CRP) showed a strong familial aggregation, with plasma glucose having the highest heritability (89%). Overall, 4 LPL loss-of-function mutations were detected (p.Asp9Asn, p.Ser45Asn, p.Asn291Ser, p.Leu365Val) and their cumulative prevalence was higher in AD than in control children (0.073 vs. 0.026; P=0.038). The LPL p.S447* gain-of-function mutation, resulted to be less frequent in AD than in control children (0.064 vs. 0.126; P=0.082). No variant in the APOA1 gene was found. Our data indicate that AD is a rather common dyslipidemia in childhood; it associates with metabolic abnormalities typical of insulin resistant state and shows a strong familial aggregation. LPL variants may contribute to the development of AD phenotype.
authors.affiliation: Department of Internal Medicine and Allied Sciences, Atherosclerosis Unit, Sapienza University of Rome, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Montali
authors.affiliation: Department of Internal Medicine and Allied Sciences, Atherosclerosis Unit, Sapienza University of Rome, Rome, Italy; Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Gessica
authors.initials: G
authors.lastname: Truglio
authors.affiliation: Department of Pediatrics, Sapienza University of Rome, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Martino
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ceci
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Ferraguti
authors.affiliation: Department of Internal Medicine and Allied Sciences, Atherosclerosis Unit, Sapienza University of Rome, Rome, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Ciociola
authors.affiliation: Department of Internal Medicine and Allied Sciences, Atherosclerosis Unit, Sapienza University of Rome, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Maranghi
authors.affiliation: Centro Ricerche Epidemiologia e Medicina Preventiva, Università dell'Insubria, Varese, Italy; Department of Epidemiology and Prevention, Laboratory of Molecular and Nutritional Epidemiology, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico Mediterraneo, Pozzilli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gianfagna
authors.affiliation: Department of Epidemiology and Prevention, Laboratory of Molecular and Nutritional Epidemiology, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Neurologico Mediterraneo, Pozzilli, Italy.
authors.forename: Licia
authors.initials: L
authors.lastname: Iacoviello
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Strom
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy; Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lucarelli
authors.affiliation: Department of Internal Medicine and Allied Sciences, Atherosclerosis Unit, Sapienza University of Rome, Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Arca
mesh_terms: D000293:Adolescent; D016632:Apolipoprotein A-I / Q000235:genetics*; D001055:Apolipoproteins B / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D050171:Dyslipidemias / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009765:Obesity / Q000150:complications
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D002097:C-Reactive Protein; C548261:LPL protein, human; D008071:Lipoprotein Lipase