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


METHODS
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.
Department of Internal Medicine and Endocrinology EMGO Institute for Health and Care Research, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. rt.dejongh@vumc.nl
Renate T
RT
de Jongh
Paul
P
Lips
Kelly J
KJ
Rijs
Natasja M
NM
van Schoor
Mark H H
MH
Kramer
Jan P
JP
Vandenbroucke
Olaf M
OM
Dekkers
D000368:Aged; D000369:Aged, 80 and over; D000071616:CDX2 Transcription Factor; D002318:Cardiovascular Diseases / Q000235:genetics / Q000401:mortality; D015331:Cohort Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D009369:Neoplasms / Q000235:genetics / Q000401:mortality; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People / Q000235:genetics*
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D018167:Receptors, Calcitriol; C062090:aminophenylacetylleucine; C053864:endodeoxyribonuclease BsmI; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases; D007930:Leucine