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Jongh, R.T. de; Lips, P.; Rijs, K.J.; Schoor, N.M. van; Kramer, M.H.H.; Vandenbroucke, J.P.; Dekkers, O.M. (2011)

Associations between vitamin D receptor genotypes and mortality in a cohort of older Dutch individuals

Article / Letter to editor
Context: Vitamin D receptor (VDR) polymorphisms are associated with a variety of diseases, which may translate into an effect on mortality. Objective: To investigate the associations between VDR gene variants and mortality among older people. Design: The analyses were conducted in a population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. Adequate DNA analysis was performed in 923 men and women (>= 65 years). We aimed to assess the associations between mortality and the VDR polymorphism FokI, three haplotypes of the Cdx2 and GATA polymorphisms, and three haplotypes of the BsmI, ApaI, and TaqI polymorphisms. Results: During the median follow-up of 10.7 years, 480 participants deceased (51%). Homozygosity for the Cdx2-GATA haplotype 1 allele was associated with a 30% higher mortality risk compared to the absence of alleles (hazard ratios (HR) 1.30, 95% confidence intervals (CI) 1.01-1.68). Adjustment for cardiovascular risk factors and 25-hydroxyvitamin D levels...Show moreContext: Vitamin D receptor (VDR) polymorphisms are associated with a variety of diseases, which may translate into an effect on mortality. Objective: To investigate the associations between VDR gene variants and mortality among older people. Design: The analyses were conducted in a population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. Adequate DNA analysis was performed in 923 men and women (>= 65 years). We aimed to assess the associations between mortality and the VDR polymorphism FokI, three haplotypes of the Cdx2 and GATA polymorphisms, and three haplotypes of the BsmI, ApaI, and TaqI polymorphisms. Results: During the median follow-up of 10.7 years, 480 participants deceased (51%). Homozygosity for the Cdx2-GATA haplotype 1 allele was associated with a 30% higher mortality risk compared to the absence of alleles (hazard ratios (HR) 1.30, 95% confidence intervals (CI) 1.01-1.68). Adjustment for cardiovascular risk factors and 25-hydroxyvitamin D levels did not affect this HR. The number of copies of the Cdx2-GATA haplotype 1 allele was associated, although not significantly, with an increased risk of osteoporotic fractures (0 copies = reference, HR, 95% CI: 1 copy 2.01, 0.99-4.07 and 2 copies 1.81, 0.87-4.18). After adjustment for osteoporotic fractures, homozygosity for the Cdx2-GATA haplotype 1 allele was no longer associated with higher mortality risk (HR 1.08, 95% CI 0.83 1.41). Conclusions: The Cdx2-GATA haplotype 1 allele was related to increased mortality risk, which may be partly explained by osteoporotic fractures. As the biological mechanism is uncertain and this study size is limited, our results should be interpreted as hypothesis generating.Show less
describing metabolic syndrome bone-mineral density gene polymorphisms linkage disequilibrium osteoporotic fracture multiple-sclerosis bsmi polymorphism disease risk population
All authors
Jongh, R.T. de; Lips, P.; Rijs, K.J.; Schoor, N.M. van; Kramer, M.H.H.; Vandenbroucke, J.P.; Dekkers, O.M.
Date
2011-01-31
Journal
European Journal of Endocrinology
Volume
164
Issue
1
Pages
75 - 82