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 (h2) 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.

Atherogenic dyslipidemia in children: evaluation of clinical, biochemical and genetic aspects / Montali, Anna; Truglio, Gessica; Martino, Francesco; Ceci, Fabrizio; Ferraguti, Giampiero; Ciociola, Ester; Maranghi, Marianna; F., Gianfagna; L., Iacoviello; Strom, Roberto; Lucarelli, Marco; Arca, Marcello. - In: PLOS ONE. - ISSN 1932-6203. - ELETTRONICO. - 10:4(2015), pp. 10(4):e0120099-10(4):e0120099. [10.1371/journal.pone.0120099]

Atherogenic dyslipidemia in children: evaluation of clinical, biochemical and genetic aspects.

MONTALI, Anna;TRUGLIO, GESSICA;MARTINO, Francesco;CECI, Fabrizio;FERRAGUTI, Giampiero;CIOCIOLA, ESTER;MARANGHI, MARIANNA;STROM, Roberto;LUCARELLI, Marco;ARCA, Marcello
2015

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 (h2) 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.
Atherogenic dyslipidemia; Lipoprotein; Metabolic syndrome; Polymorphisms
01 Pubblicazione su rivista::01a Articolo in rivista
Atherogenic dyslipidemia in children: evaluation of clinical, biochemical and genetic aspects / Montali, Anna; Truglio, Gessica; Martino, Francesco; Ceci, Fabrizio; Ferraguti, Giampiero; Ciociola, Ester; Maranghi, Marianna; F., Gianfagna; L., Iacoviello; Strom, Roberto; Lucarelli, Marco; Arca, Marcello. - In: PLOS ONE. - ISSN 1932-6203. - ELETTRONICO. - 10:4(2015), pp. 10(4):e0120099-10(4):e0120099. [10.1371/journal.pone.0120099]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/781986
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