Serum 25-Hydroxyvitamin D, Plasma Lipids, and Associated Gene Variants in Prepubertal Children

J Clin Endocrinol Metab. 2018 Jul 1;103(7):2670-2679. doi: 10.1210/jc.2018-00335.

Abstract

Context: The associations of serum 25-hydroxyvitamin D [25(OH)D] with plasma lipids remain controversial in children.

Objective: To examine the associations and interactions of 25(OH)D and related gene variants with lipids in children.

Design: Cross-sectional.

Setting: Kuopio, Finland.

Participants: Population sample of 419 prepubertal white children aged 6 to 8 years.

Main outcome measures: 25(OH)D, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides.

Results: Serum 25(OH)D was negatively associated with total cholesterol (β = -0.141, P = 0.004), LDL cholesterol (β = -0.112, P = 0.023), HDL cholesterol (β = -0.150, P = 0.002), and triglycerides (β = -0.104, P = 0.035) adjusted for age and sex. Associations of 25(OH)D with total cholesterol, LDL cholesterol, and HDL cholesterol remained after adjustment for adiposity, physical activity, sedentary behavior, diet, daylight time, and parental education. Children in the highest quartile of 25(OH)D had the lowest total cholesterol (P = 0.022) and LDL cholesterol (P = 0.026) adjusted for age and sex. Cytochrome P450 family 2 subfamily R member 1 (CYP2R1) rs12794714, CYP2R1 rs10741657, and vitamin D binding protein (DBP) rs2282679 were associated with 25(OH)D adjusted for age and sex. CYP2R1 rs12794714 was associated with total cholesterol and LDL cholesterol and C10orf88 rs6599638 with HDL cholesterol adjusted for age, sex, and 25(OH)D. The gene variants did not explain or modify the associations of 25(OH)D with lipids.

Conclusions: 25(OH)D was independently and inversely associated with total cholesterol, LDL cholesterol, and HDL cholesterol. CYP2R1 rs12794714, CYP2R1 rs10741657, and DBP rs2282679 were associated with 25(OH)D. CYP2R1 rs12794714 was associated with total cholesterol and LDL cholesterol and chromosome 10 open reading frame 88 (C10orf88) rs6599638 with HDL cholesterol independent of 25(OH)D. None of the gene variants modified the associations of 25(OH)D with lipids. Further studies are needed to detect the mechanisms for the associations of 25(OH)D with lipids.

Trial registration: ClinicalTrials.gov NCT01803776.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity
  • Child
  • Cholestanetriol 26-Monooxygenase / blood
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cross-Sectional Studies
  • Cytochrome P450 Family 2 / blood
  • Exercise
  • Female
  • Finland
  • Genetic Variation*
  • Humans
  • Lipids / blood*
  • Male
  • Sedentary Behavior
  • Triglycerides / blood
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D-Binding Protein / blood

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • GC protein, human
  • Lipids
  • Triglycerides
  • Vitamin D-Binding Protein
  • Vitamin D
  • Cholesterol
  • 25-hydroxyvitamin D
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • Cholestanetriol 26-Monooxygenase

Associated data

  • ClinicalTrials.gov/NCT01803776