Nutritional Effects of .GAMMA.-Glutamyl Carboxylase Gene Polymorphism on the Correlation between the Vitamin K Status and .GAMMA.-Carboxylation of Osteocalcin in Young Males

Abstract

Summary Vitamin K is a cofactor for ␥ -glutamyl carboxylase (GGCX), which is an essential enzyme for the ␥ -carboxylation of vitamin K-dependent proteins such as osteocalcin (OC). Associations among dietary vitamin K intake, vitamin K status, and bone metabolism have not been thoroughly investigated. Recently, it has been reported that single nucleotide polymorphisms of GGCX (R325Q, 974G Ͼ A) were associated with age-related bone loss and the kinetic affinity for the substrate. In the present study, we investigated the associations among dietary vitamin K intake, the level of serum vitamin K, and the ratio of undercarboxylated OC (ucOC) to intact OC. The subjects were 60 healthy young male volunteers (mean age, 22.6 y; standard deviation, 1.6). Dietary nutrient intake was assessed by consecutive individual 3-d food records taken before the day of blood examinations. Serum concentrations of vitamin K (phylloquinone: PK, menaquinone 4: MK-4, and menaquinone 7: MK-7), ucOC, and intact OC were measured. All subjects were genotyped for polymorphism (R325Q) presence. Dietary vitamin K intake from vegetables was significantly correlated with the level of serum PK, and vitamin K intake from fermented beans, natto, was also significantly correlated with the level of serum MK-7. The ratio of ucOC to intact OC showed a negative association with the total vitamin K intake ( r ϭϪ 0.331, p ϭ 0.010) and serum MK-7 ( r ϭϪ 0.394, p ϭ 0.002). Interestingly, grouped by the GGCX genotype, a significant interaction between the ratio of ucOC to intact OC with serum MK-7 was observed in 325R homozygotes ( r ϭϪ 0.572, p ϭ 0.003), but not in heterozygotes, nor in 325Q homozygotes. This is the first report to suggest the effects of the single nucleotide polymorphism R325Q in the GGCX gene on the correlation between the level of serum MK-7 and ␥ -carboxylation of serum OC.

Osteocalcin Is Not Associated with the Risk of Type 2 Diabetes: Findings from the EPIC-NL Study

“…Previous studies suggested %ucOC as a marker of vitamin K intake, but we could not confirm these findings. The correlation between %ucOC and vitamin K intake in our study was much lower than in previous studies, which showed correlations of -0.21 and -0.33 respectively [ 25 , 26 ]. However, in these studies vitamin K intake was measured with 3 day food- records before the day of blood examination [ 25 , 26 ].…”

“…The correlation between %ucOC and vitamin K intake in our study was much lower than in previous studies, which showed correlations of -0.21 and -0.33 respectively [ 25 , 26 ]. However, in these studies vitamin K intake was measured with 3 day food- records before the day of blood examination [ 25 , 26 ]. The validity of the FFQ may explain the difference between our study and previous studies.…”

Analysis of Osteocalcin as a Candidate Gene for Type 2 Diabetes (T2D) and Intermediate Traits in Caucasians and African Americans

“…In humans, γ-carboxylation is controlled by the vitamin K dependent enzyme γ-glutamyl carboxylase (GGCX). Functional polymorphisms of GGCX and the vitamin K epoxide reductase (VKORC1) gene were associated with uncarboyxlated OCN levels [17,24]. Transcriptional regulation of BGLAP in humans is controlled by promoter binding of a complex that includes the transcription factor RUNX2, coactivator CBP/p300, and corepressor HDAC3 at the promoter [15,21].…”

Low Serum Levels of Undercarboxylated Osteocalcin in Postmenopausal Osteoporotic Women Receiving an Inhibitor of Bone Resorption

“…The fraction of OC that has undergone imperfect gamma-carboxylation is referred to as undercarboxylated OC (ucOC), and cannot be shifted from blood vessels to bone due to a decrease in the affinity for Ca 2+ and hydroxyapatite (Hauschka et al 1989). Since vitamin K is involved in this carboxylation, inadequate levels of vitamin K lead to increased serum ucOC levels (Sokoll and Sadowski 1996;Binkley et al 2002;Sogabe et al 2007). Serum ucOC levels are thus regarded as a marker of vitamin K deficiency.…”