Genetic and non-genetic correlates of vitamins K and D

Eur J Clin Nutr. 2009 Apr;63(4):458-64. doi: 10.1038/sj.ejcn.1602959. Epub 2007 Nov 21.


Objective: To assess the genetic and nongenetic correlates of circulating measures of vitamins K and D status in a community-based sample of men and women.

Subjects/methods: A cross-sectional study of 1762 participants of the Framingham Offspring Study (919 women; mean age 59 years). Vitamin K status was measured as plasma phylloquinone and serum percent undercarboxylated osteocalcin (ucOC), and vitamin D was measured using plasma 25-hydroxyvitamin D (25(OH)D). Associations between vitamin K status and vitamin D status with biologically plausible nongenetic factors were assessed using stepwise regression. Heritability and linkage were determined using Sequential Oligogenic Linkage Analysis Routines (SOLAR).

Results: Nongenetic factors accounted for 20.1 and 12.3% of the variability in plasma phylloquinone in men and women respectively, with triglycerides and phylloquinone intake being the primary correlates. In men 12.2% and in women 14.6% of the variability in %ucOC was explained by nongenetic factors in our models. Heritability estimates for these vitamin K status biomarkers were nonsignificant. Season, vitamin D intake, high-density lipoprotein (HDL) cholesterol and waist circumference explained 24.7% (men) and 24.2% (women) of the variability in plasma 25(OH)D. Of the three vitamins examined, only 25(OH)D was significantly heritable (heritability estimate=28.8%, P<0.01), but linkage analysis of 25(OH)D did not achieve genome-wide significance.

Conclusions: Variability in biomarkers of vitamin K status was attributed to nongenetic factors, whereas plasma 25(OH)D was found to be significantly heritable. Further studies are warranted to investigate genetic loci influencing vitamin D status.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Aged
  • Biomarkers / blood
  • Creatinine / blood
  • Cross-Sectional Studies
  • Female
  • Genetic Linkage
  • Humans
  • Hypertension / blood
  • Hypolipidemic Agents
  • Lipids / blood
  • Male
  • Menopause
  • Middle Aged
  • Osteocalcin* / blood
  • Osteocalcin* / genetics
  • Quantitative Trait, Heritable*
  • Smoking
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / genetics
  • Vitamin K 1 / blood*
  • Vitamin K* / blood
  • Vitamin K* / genetics
  • Vitamins* / blood
  • Vitamins* / genetics
  • Waist Circumference


  • Biomarkers
  • Hypolipidemic Agents
  • Lipids
  • Vitamins
  • Osteocalcin
  • Vitamin K
  • Vitamin D
  • Vitamin K 1
  • 25-hydroxyvitamin D
  • Creatinine