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The associations of 25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms, and race with risk of incident fracture-related hospitalization: Twenty-year follow-up in a bi-ethnic cohort (the ARIC Study).
Bone. 2015 Sep; 78:94-101.BONE

Abstract

BACKGROUND

Deficient levels of 25-hydroxyvitamin D [25(OH)D] have been associated with increased fracture risk. Racial differences in fracture risk may be related to differences in bioavailable vitamin D due to single nucleotide polymorphism (SNP) variations in the vitamin D binding protein (DBP).

METHODS

We measured 25(OH)D levels in 12,781 middle-aged White and Black participants [mean age 57 years (SD 5.7), 25% Black] in the ARIC Study who attended the second examination from 1990-1992. Participants were genotyped for two DBP SNPs (rs4588 and rs7041). Incident hospitalized fractures were measured by abstracting hospital records for ICD-9 codes. We used Cox proportional hazards models to evaluate the association between 25(OH)D levels and risk of fracture with adjustment for possible confounders. Interactions were tested by race and DBP genotype.

RESULTS

There were 1122 incident fracture-related hospitalizations including 267 hip fractures over a median of 19.6 years of follow-up. Participants with deficient 25(OH)D (<20 ng/mL) had a higher risk of any fracture hospitalization [HR=1.21 (95% CI 1.05-1.39)] and hospitalization for hip fracture [HR=1.35 (1.02-1.79)]. No significant racial interaction was noted (p-interaction=0.20 for any fracture; 0.74 for hip fracture). There was no independent association of rs4588 and rs7041 with fracture. However, there was a marginal interaction for 25(OH)D deficiency with rs7041 among Whites (p-interaction=0.065). Whites with both 25(OH)D deficiency and the GG genotype [i.e., with predicted higher levels of DBP and lower bioavailable vitamin D] were at the greatest risk for any fracture [HR=1.48 (1.10-2.00)] compared to Whites with the TT genotype and replete 25(OH)D (reference group).

CONCLUSIONS

Deficient 25(OH)D levels are associated with higher incidence of hospitalized fractures. Marginal effects were seen in Whites for the DBP genotype associated with lower bioavailable vitamin D, but result inconclusive. Further investigation is needed to more directly evaluate the association between bioavailable vitamin D and fracture risk.

Authors+Show Affiliations

Northeast Ohio Medical University, Akron, OH, USA.Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MD, USA.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: edonnell@jhmi.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25920689

Citation

Takiar, Radhika, et al. "The Associations of 25-hydroxyvitamin D Levels, Vitamin D Binding Protein Gene Polymorphisms, and Race With Risk of Incident Fracture-related Hospitalization: Twenty-year Follow-up in a Bi-ethnic Cohort (the ARIC Study)." Bone, vol. 78, 2015, pp. 94-101.
Takiar R, Lutsey PL, Zhao D, et al. The associations of 25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms, and race with risk of incident fracture-related hospitalization: Twenty-year follow-up in a bi-ethnic cohort (the ARIC Study). Bone. 2015;78:94-101.
Takiar, R., Lutsey, P. L., Zhao, D., Guallar, E., Schneider, A. L., Grams, M. E., Appel, L. J., Selvin, E., & Michos, E. D. (2015). The associations of 25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms, and race with risk of incident fracture-related hospitalization: Twenty-year follow-up in a bi-ethnic cohort (the ARIC Study). Bone, 78, 94-101. https://doi.org/10.1016/j.bone.2015.04.029
Takiar R, et al. The Associations of 25-hydroxyvitamin D Levels, Vitamin D Binding Protein Gene Polymorphisms, and Race With Risk of Incident Fracture-related Hospitalization: Twenty-year Follow-up in a Bi-ethnic Cohort (the ARIC Study). Bone. 2015;78:94-101. PubMed PMID: 25920689.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The associations of 25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms, and race with risk of incident fracture-related hospitalization: Twenty-year follow-up in a bi-ethnic cohort (the ARIC Study). AU - Takiar,Radhika, AU - Lutsey,Pamela L, AU - Zhao,Di, AU - Guallar,Eliseo, AU - Schneider,Andrea L C, AU - Grams,Morgan E, AU - Appel,Lawrence J, AU - Selvin,Elizabeth, AU - Michos,Erin D, Y1 - 2015/04/25/ PY - 2015/01/12/received PY - 2015/03/22/revised PY - 2015/04/20/accepted PY - 2015/4/30/entrez PY - 2015/4/30/pubmed PY - 2016/4/9/medline KW - Epidemiology KW - Fracture KW - Race KW - Vitamin D KW - Vitamin D binding protein polymorphisms SP - 94 EP - 101 JF - Bone JO - Bone VL - 78 N2 - BACKGROUND: Deficient levels of 25-hydroxyvitamin D [25(OH)D] have been associated with increased fracture risk. Racial differences in fracture risk may be related to differences in bioavailable vitamin D due to single nucleotide polymorphism (SNP) variations in the vitamin D binding protein (DBP). METHODS: We measured 25(OH)D levels in 12,781 middle-aged White and Black participants [mean age 57 years (SD 5.7), 25% Black] in the ARIC Study who attended the second examination from 1990-1992. Participants were genotyped for two DBP SNPs (rs4588 and rs7041). Incident hospitalized fractures were measured by abstracting hospital records for ICD-9 codes. We used Cox proportional hazards models to evaluate the association between 25(OH)D levels and risk of fracture with adjustment for possible confounders. Interactions were tested by race and DBP genotype. RESULTS: There were 1122 incident fracture-related hospitalizations including 267 hip fractures over a median of 19.6 years of follow-up. Participants with deficient 25(OH)D (<20 ng/mL) had a higher risk of any fracture hospitalization [HR=1.21 (95% CI 1.05-1.39)] and hospitalization for hip fracture [HR=1.35 (1.02-1.79)]. No significant racial interaction was noted (p-interaction=0.20 for any fracture; 0.74 for hip fracture). There was no independent association of rs4588 and rs7041 with fracture. However, there was a marginal interaction for 25(OH)D deficiency with rs7041 among Whites (p-interaction=0.065). Whites with both 25(OH)D deficiency and the GG genotype [i.e., with predicted higher levels of DBP and lower bioavailable vitamin D] were at the greatest risk for any fracture [HR=1.48 (1.10-2.00)] compared to Whites with the TT genotype and replete 25(OH)D (reference group). CONCLUSIONS: Deficient 25(OH)D levels are associated with higher incidence of hospitalized fractures. Marginal effects were seen in Whites for the DBP genotype associated with lower bioavailable vitamin D, but result inconclusive. Further investigation is needed to more directly evaluate the association between bioavailable vitamin D and fracture risk. SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/25920689/The_associations_of_25_hydroxyvitamin_D_levels_vitamin_D_binding_protein_gene_polymorphisms_and_race_with_risk_of_incident_fracture_related_hospitalization:_Twenty_year_follow_up_in_a_bi_ethnic_cohort__the_ARIC_Study__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(15)00142-8 DB - PRIME DP - Unbound Medicine ER -