Submitted to: Journal of Bone and Mineral Research
Publication Type: Abstract Only
Publication Acceptance Date: 7/25/2005
Publication Date: 9/1/2005
Citation: Crosier, M.D., Shea, M.K., Ordovas, J.M., Gundberg, C.M., Dawson-Hughes, B., Booth, S.L. 2005. Apolipoprotein E genotype is a determinant of serum vitamin K, but not BMD (bone marrow density), in older men and women [abstract]. Journal of Bone and Mineral Research. 20:S343.
Technical Abstract: Apolipoprotein E (/APOE/) is a determinant of triglyceride-rich lipoprotein (TRL) clearance, and has a potential role in the regulation of bone formation. Vitamin K is a cofactor for the gamma-carboxylation of osteocalcin, and is carried by TRL. It has been proposed that /APOE/’s role in bone formation is mediated through the delivery of the fat-soluble vitamin K to osteoblasts. Cross-sectional associations of /APOE/ with biochemical measures of vitamin K status [serum phylloquinone (vitamin K-1) and percent undercarboxylated osteocalcin (%ucOC)] were examined in 407 older men and women (mean age:68y; 60% women) selected for low vitamin K intake (<100 mg/day) as criteria for participation in a vitamin K clinical trial. All subjects had bone mineral density (BMD) of the hip, spine and total body measured by DXA. /APOE/ was genotyped using a Taqman probe-based 5’ nuclease assay. The distribution of the /APOE/ genotypes were 3/3 263 (64.6%); 3/4 79 (19.4%); 2/3 47 (11.5%); 4/4 7 (7.1%) 2/4 11 (2.7%). All analyses were conducted at baseline, prior to randomization in the clinical trial. /APOE/ genotype was significantly associated with serum phylloquinone concentrations (p=0.04), independent of serum triglycerides. Those with the E2/3 genotype had higher serum phylloquinone concentrations [mean (SD) 1.96 (2.65) nmol/L] compared to those with other genotypes (range of means: 0.94 to 1.17 nmol/L) (p=0.02). There was no association of /APOE/ genotype with %ucOC or with BMD at any anatomical site. However, /APOE/ genotype was associated with total osteocalcin concentrations (p=0.001); those with the E4/4 genotype had higher serum total osteocalcin concentrations [mean (SD) 12.6 (5.50) ng/mL] compared to those with other genotypes (range of means: 7.1-8.4 ng/ml). Limitations of this study are its cross-sectional design, small sample size and the potential for selection bias as these were primarily Caucasian individuals with low vitamin K intake. In conclusion, /APOE/ genotype may be a non-dietary determinant of serum phylloquinone concentrations in older men and women. /APOE/ genotype is also associated with serum concentrations of osteocalcin, which is a marker of bone formation, but not %ucOC, which is a marker of vitamin K status. The role of /APOE/ genotype in the response of age-related bone loss to vitamin K supplementation needs to be determined.