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B-vitamins and their interaction with the MTHFR C677 T genotype as determinants of bone health in older adults from the TUDA Ageing cohort study

Published online by Cambridge University Press:  24 November 2016

M. Clarke ,
M. Ward ,
L. Hoey ,
J.J. Strain ,
A. Molloy ,
E. Laird ,
M. Healy ,
M.C. Casey ,
C. Cunningham  and
M.T. McCann
...Show all authors
M. Clarke
Affiliation:
Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, BT52 1SA UCD Institute of Food and Health, Belfield, University College Dublin, Dublin 4, Ireland
M. Ward
Affiliation:
Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, BT52 1SA
L. Hoey
Affiliation:
Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, BT52 1SA
J.J. Strain
Affiliation:
Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, BT52 1SA
A. Molloy
Affiliation:
School of Medicine, Trinity College Dublin 2, Ireland
E. Laird
Affiliation:
School of Medicine, Trinity College Dublin 2, Ireland
M. Healy
Affiliation:
The Department of Clinical Biochemistry, Central Pathology, St James's Hospital, Dublin, Ireland
M.C. Casey
Affiliation:
The Mercers Institute for Research on Ageing, St James's Hospital, Dublin, Ireland
C. Cunningham
Affiliation:
The Mercers Institute for Research on Ageing, St James's Hospital, Dublin, Ireland
M.T. McCann
Affiliation:
Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, BT52 1SA
H. McNulty
Affiliation:
Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, BT52 1SA
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Abstract

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This abstract was presented as the Public Health Nutrition Theme highlight.

Osteoporosis, characterised by reduced bone mineral density (BMD) and a high risk of fragility fracture, is increasingly prevalent in today's ageing society(Reference Strom, Borgstrom and Kanis1). Large observational studies support a protective role for certain B-vitamins integral to 1-carbon metabolism (i.e. folate, vitamins B12, B6 and riboflavin) against osteoporosis(Reference Dai and Koh2). A common polymorphism (C677 T) in the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) has also been linked to osteoporosis, with a heightened risk demonstrated in the presence of low B-vitamin status(2). However, previous studies exploring the role of this polymorphism have tended to overlook relevant gene-nutrient interactions(2). The aim of this investigation was to examine the interaction of relevant B-vitamin biomarkers with the MTHFR 677TT genotype as determinants of low BMD.

Older adults (n 3,127) recruited to the Trinity Ulster Department of Agriculture (TUDA) Ageing cohort study, and with BMD measured by dual energy X-ray absorptiometry scans, were investigated. Low BMD was defined as a combination of osteopenia (T-Score; between −1 and −2·5 SD) and osteoporosis (T-Score; −2·5 SD or less).

Age (p < 0·001), physical inactivity (p = 0·015), and parathyroid hormone (p < 0·001) were associated with an increased risk of low BMD, while increasing body weight (p < 0·001) reduced the risk. The MTHFR C677 T genotype was not found to be a significant predictor of low BMD in either males or females. Females with the MTHFR 677TT genotype in combination with low biomarker status of riboflavin or folate had a two-fold increased risk of low BMD compared to those with the MTHFR 677CC genotype and optimal B-vitamin status, after adjustment for covariates; these associations were not observed in men (Table).

Table.

Predictors of low bone mineral density ‘BMD’ (osteoporosis and osteopenia combined)

Analysis by binary logistic regression, comparing lowest tertile of vitamin status to the other tertiles combined. Reference category; MTHFR 677CC genotype and highest B-vitamin status. Riboflavin was measured using erythrocyte glutathionine reductase activation coefficient ‘EGRac’. Folate was measured in red blood cells by microbiological assay.

These findings suggest that there are important gene-nutrient interactions within 1-carbon metabolism that appear to play an important role in maintaining bone health throughout life.

Acknowledgement of Funding: Food for Health Research Initiative of the Irish Department of Agriculture and Health Research Board, with co-funding from the Department for Employment and Learning Northern Ireland under its Cross-Border Research and Development Programme: “Strengthening the all-Island Research Base”.

References

1.Strom, O, Borgstrom, F, Kanis, JA et al. (2011) Arch Osteoporos 6, 59–155.10.1007/s11657-011-0060-1Google Scholar
2.Dai, & Koh, (2015) Nutrients, 7, 3322–3346.10.3390/nu7053322Google Scholar
Figure 0

Table. Predictors of low bone mineral density ‘BMD’ (osteoporosis and osteopenia combined)