Ethnic differences in osteocalcin γ-carboxylation, plasma phylloquinone (vitamin K1) and apolipoprotein E genotype

Abstract

Objective: To investigate plasma osteocalcin g-carboxylation and its relationship to plasma phylloquinone concentration and apolipoprotein E (apoE) genotype in women from three ethnic groups with differing osteoporotic fracture risk. Design and subjects: Fasted blood samples were collected from postmenopausal Gambian (n ¼ 50), British (n ¼ 31) and Chinese women (n ¼ 23), and 11 premenopausal women in each group from three cross-sectional studies. Results: After adjustment for total osteocalcin, plasma undercarboxylated osteocalcin (adjusted ucOC) was lowest in Chinese and highest in British women postmenopause (British vs Chinese 103% higher, Po0.0001; Gambian vs Chinese 66% higher, Po0.01). No differences were observed premenopause. Within each ethnic group, adjusted ucOC was similar pre-and postmenopause. Postmenopause, plasma phylloquinone was higher in Chinese women (1.0 ng/ml) than in British (0.31 ng/ml) and Gambian women (0.36 ng/ml) (Po0.0001). Premenopause, plasma phylloquinone was higher in Gambian and Chinese women (0.6 ng/ml) than in British women (0.3 ng/ml; P ¼ 0.01). Plasma phylloquinone and adjusted ucOC were inversely related in postmenopausal British women (R 2 ¼ 32.4%; P ¼ 0.0008). ApoE4 frequency was Gambian 32.6%, British 13.8% and Chinese 6%. A lower adjusted ucOC was associated with apoE2 genotype in British and Chinese women. Ethnic differences in adjusted ucOC persisted after adjustment for phylloquinone and apoE genotype. Conclusion: These preliminary data indicate suboptimal vitamin K status in postmenopausal British compared to Chinese and Gambian women. Ethnic differences in apoE genotype may also influence osteocalcin g-carboxylation status. The study highlights the need for larger epidemiological investigations of ethnic differences in vitamin K status and the possible implications to bone health. Sponsorship: This work was funded by the MRC.

Vitamins K and D Status in Stages 3–5 Chronic Kidney Disease

“…In our study, the only significant independent association we found was between the apoE4 allele and higher PIVKA-II concentrations. At present, the direction and magnitude of the effect of apoE genotype on ␥-carboxylation status of peripheral VKDPs remain controversial (11,12). However, this study and our earlier study suggest that the apoE4 allele may be associated with poorer ␥-carboxylation of VKDPs in individuals with CKD.…”

“…Vitamin K status may also be determined by variations in the genes involved in the transport or uptake of vitamin K into liver and bone (apolipoprotein E (apoE)) or those involved in the tissue-specific recycling of vitamin K (Vitamin K Epoxide Reductase (VKOR)). There are few studies evaluating the effect of variations within these two genes and vitamin K status in either the general population or in those with CKD (6,(11)(12)(13).…”

Apolipoprotein E genotype may influence urinary gammacarboxyglutamate (Gla) concentrations in young individuals

“…The most important finding in this paper was that the apo E genotype is a major determinant in urinary Gla excretion, which is consistent with observations that also serum vitamin K levels ) and the extent of osteocalcin carboxylation are strongly dependent on the apo E genotype (Beavan et al 2005;Pilkey et al 2007). …”

Determinants and Correlates of Serum Undercarboxylated Osteocalcin

“…While 1 study reported decreasing ucOC concentrations in men and women with age [7] , 2 studies found no age effect in males or females [18,19] , and 2 other studies showed increasing concentrations with age in women [20,21] . The osteoblastic activity is age dependent, leading to changes in osteocalcin synthesis with age [22] .…”