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

Authors: de Jongh RT; Lips P; Rijs KJ; van Schoor NM; Kramer MH; Vandenbroucke JP; Dekkers OM

Abstract: 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 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.

Keywords: Aged; Aged, 80 and over; Cardiovascular Diseases/genetics/mortality; Cohort Studies; Deoxyribonucleases, Type II Site-Specific/*genetics; European Continental Ancestry Group/*genetics; Female; Genetic Predisposition to Disease; Genotype; *Haplotypes; Homeodomain Proteins/*genetics; Humans; Leucine/*analogs & derivatives/genetics; Male; Middle Aged; *Mortality/trends; Neoplasms/genetics/mortality; Netherlands/epidemiology; Odds Ratio; *Polymorphism, Genetic; Receptors, Calcitriol/*genetics; Risk Assessment; Risk Factors
Journal: European journal of endocrinology / European Federation of Endocrine Societies
Volume: 164
Issue: 1
Pages: 75-82
Date: Nov. 6, 2010
PMID: 21051524
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Citation:

de Jongh RT, Lips P, Rijs KJ, van Schoor NM, Kramer MH, Vandenbroucke JP, Dekkers OM (2011) Associations between vitamin D receptor genotypes and mortality in a cohort of older Dutch individuals. European journal of endocrinology / European Federation of Endocrine Societies 164: 75-82.


Longevity Variant Associations (p-value):
  • Cdx2–GATA haplotypes (0.05)
  • Cdx2-GATA haplotype 1 allele (0.78)

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