BackgroundThe DLK1 human gene encodes for the transmembrane EGF-like repeat-containing protein DLK1, which acts as a modulator of adipogenesis. A role for DLK1 in energy metabolism and lipid homeostasis has been suggested and DLK1 gene variants have been related to pubertal development.ObjectiveThe aim of this study was to uncover DLK1 SNPs in a cohort of children and analyze their relationship with anthropometric and biochemical variables.MethodsOur population-based sample comprises 1237 healthy 6-to-8-year-old Caucasian children. The presence of five DLK1 SNPs (rs1802710, rs876374, rs7155375, rs57098752, and rs7149242) was analyzed by Real-Time PCR, using predesigned TaqMan (TM) Genotyping Assays.ResultsWe observed that the SNPs rs1802710 and rs876374 were associated with BMI, and the prevalence of these two SNPs was different in normal-weight children compared to children with obesity. Related to biochemical variables, we found a significant association of the SNPs rs1802710, rs876374, and rs57098752 and their combination with Apo-B plasma concentrations after adjusting by BMI and sex. The SNPs rs1802710 and rs57098752 were also significantly associated with plasma levels of LDL-C and HDL-C, respectively.ConclusionOur study reveals that DLK1 gene variants may influence both body weight and lipid homeostasis, affecting particularly to the Apo-B biology, in children.Impact polymorphisms are associated with BMI and with lipid levels, independently of BMI, early in life.Our data add to the existing literature the evidence that gene variants impact on lipid metabolism.The confirmation at the population level that genetic variants are associated with anthropometric and lipid variables sustains the role of DLK1 in obesity and related disorders and should lead to further studies aimed at clarifying this effect.
机构:
Childrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USAChildrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
Vajravelu, Mary Ellen
Lee, Joyce M.
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Univ Michigan, Susan B Meister Child Hlth Evaluat & Res Ctr, Div Pediat Endocrinol, Ann Arbor, MI 48109 USAChildrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
Lee, Joyce M.
Shah, Rachana
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Childrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USAChildrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
Shah, Rachana
Shults, Justine
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Childrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
Univ Penn, Dept Biostat Epidemiol & Informat, Philadelphia, PA 19104 USAChildrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
Shults, Justine
Amaral, Sandra
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Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA
Childrens Hosp Philadelphia, Div Nephrol, Philadelphia, PA 19104 USAChildrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
Amaral, Sandra
Kelly, Andrea
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Childrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USAChildrens Hosp Philadelphia, Div Endocrinol & Diabet, Philadelphia, PA 19104 USA
机构:
Univ Saskatchewan, Dept Med, Div Neurol, Royal Univ Hosp, Saskatoon, SK S7N 0W8, CanadaUniv Saskatchewan, Dept Med, Div Neurol, Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada
Tellez-Zenteno, Jose F.
Pahwa, Dave Rishi
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Univ Saskatchewan, Dept Med, Div Neurol, Royal Univ Hosp, Saskatoon, SK S7N 0W8, CanadaUniv Saskatchewan, Dept Med, Div Neurol, Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada
Pahwa, Dave Rishi
Hernandez-Ronquillo, Lizbeth
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Univ Saskatchewan, Dept Med, Div Neurol, Royal Univ Hosp, Saskatoon, SK S7N 0W8, CanadaUniv Saskatchewan, Dept Med, Div Neurol, Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada
Hernandez-Ronquillo, Lizbeth
Garcia-Ramos, Guillermo
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Natl Inst Med Sci & Nutr Salvador Zubiran, Dept Neurol & Psychiat, Mexico City, DF, MexicoUniv Saskatchewan, Dept Med, Div Neurol, Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada
Garcia-Ramos, Guillermo
Velazquez, Antonio
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Natl Inst Med Sci & Nutr Salvador Zubiran, Blood Bank, Mexico City, DF, MexicoUniv Saskatchewan, Dept Med, Div Neurol, Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada
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Indiana Univ, Sch Med, Div Endocrinol Diabet & Metab, Indianapolis, IN USAIndiana Univ, Sch Med, Div Endocrinol Diabet & Metab, Indianapolis, IN USA
Al Sabie, Farah
Tariq, Zunera
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Indiana Univ, Sch Med, Dept Internal Med, Indianapolis, IN USAIndiana Univ, Sch Med, Div Endocrinol Diabet & Metab, Indianapolis, IN USA
Tariq, Zunera
Erickson, Dana
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Mayo Clin, Div Endocrinol Diabet & Metab, Rochester, MN USAIndiana Univ, Sch Med, Div Endocrinol Diabet & Metab, Indianapolis, IN USA
Erickson, Dana
Donegan, Diane
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Indiana Univ, Sch Med, Div Endocrinol Diabet & Metab, Indianapolis, IN USA
Mayo Clin, Div Endocrinol Diabet & Metab, Rochester, MN USAIndiana Univ, Sch Med, Div Endocrinol Diabet & Metab, Indianapolis, IN USA