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Association of the VDR translation start site polymorphism and fracture risk in older women.
J Bone Miner Res. 2007 May; 22(5):730-6.JB

Abstract

We evaluated the association between the VDR translation start site polymorphism and osteoporotic phenotypes among 6698 older white women. Women with the C/C genotype had lower wrist BMD and an increased risk of wrist and all non-spine/low-trauma fractures. The high frequency of this variant confers a population attributable risk that is similar to several established risk factors for fracture.

INTRODUCTION

The vitamin D receptor (VDR) is a nuclear receptor that regulates bone formation, bone resorption, and calcium homeostasis. A common C to T polymorphism in exon 2 of the VDR gene introduces a new translation start site and a protein that differs in length by three amino acids (T = 427aa, C = 424aa; rs10735810).

MATERIALS AND METHODS

We conducted genetic association analyses of this polymorphism, BMD, and fracture outcomes in a prospective cohort of 6698 white American women >or=65 years of age. Incident fractures were confirmed by physician adjudication of radiology reports. There were 2532 incident nontraumatic/nonvertebral fractures during 13.6 yr of follow-up including 509 wrist and 703 hip fractures.

RESULTS

Women with the C/C genotype had somewhat lower distal radius BMD compared with those with the T/T genotype (CC=0.358 g/cm(2), CT=0.361 g/cm(2), TT=0.369 g/cm(2), p=0.003). The C/C genotype was also associated with increased risk of non-spine, low traumatic fractures (HR: 1.18; 95% CI: 1.04, 1.33) and wrist fractures (HR: 1.33; 95% CI: 1.01, 1.75) compared with the T/T genotype in age-adjusted models. Further adjustments for distal radius BMD only slightly attenuated these associations. The VDR polymorphism was not associated with hip fracture. The population attributable risk (PAR) of the C/C genotype for incident fractures was 6.1%. The PAR for established risk factors for fracture were: low femoral neck BMD (PAR=16.3%), maternal history of fracture (PAR=5.1%), low body weight (PAR=5.3%), corticosteroid use (PAR=1.3%), and smoking (PAR=1.6%). Similar PAR results were observed for wrist fractures.

CONCLUSIONS

The common and potentially functional VDR translation start site polymorphism confers a modestly increased relative risk of fracture among older white women. However, the high frequency of this variant confers a population attributable risk that is similar to or greater than several established risk factors for fracture.

Authors+Show Affiliations

Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. susan.moffett@hgen.pitt.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17280526

Citation

Moffett, Susan P., et al. "Association of the VDR Translation Start Site Polymorphism and Fracture Risk in Older Women." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 22, no. 5, 2007, pp. 730-6.
Moffett SP, Zmuda JM, Cauley JA, et al. Association of the VDR translation start site polymorphism and fracture risk in older women. J Bone Miner Res. 2007;22(5):730-6.
Moffett, S. P., Zmuda, J. M., Cauley, J. A., Ensrud, K. E., Hillier, T. A., Hochberg, M. C., Li, J., Cayabyab, S., Lee, J. M., Peltz, G., & Cummings, S. R. (2007). Association of the VDR translation start site polymorphism and fracture risk in older women. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 22(5), 730-6.
Moffett SP, et al. Association of the VDR Translation Start Site Polymorphism and Fracture Risk in Older Women. J Bone Miner Res. 2007;22(5):730-6. PubMed PMID: 17280526.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of the VDR translation start site polymorphism and fracture risk in older women. AU - Moffett,Susan P, AU - Zmuda,Joseph M, AU - Cauley,Jane A, AU - Ensrud,Kristine E, AU - Hillier,Teresa A, AU - Hochberg,Marc C, AU - Li,Jia, AU - Cayabyab,Shelia, AU - Lee,Jocelyn M, AU - Peltz,Gary, AU - Cummings,Steven R, PY - 2007/2/7/pubmed PY - 2007/7/21/medline PY - 2007/2/7/entrez SP - 730 EP - 6 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 22 IS - 5 N2 - UNLABELLED: We evaluated the association between the VDR translation start site polymorphism and osteoporotic phenotypes among 6698 older white women. Women with the C/C genotype had lower wrist BMD and an increased risk of wrist and all non-spine/low-trauma fractures. The high frequency of this variant confers a population attributable risk that is similar to several established risk factors for fracture. INTRODUCTION: The vitamin D receptor (VDR) is a nuclear receptor that regulates bone formation, bone resorption, and calcium homeostasis. A common C to T polymorphism in exon 2 of the VDR gene introduces a new translation start site and a protein that differs in length by three amino acids (T = 427aa, C = 424aa; rs10735810). MATERIALS AND METHODS: We conducted genetic association analyses of this polymorphism, BMD, and fracture outcomes in a prospective cohort of 6698 white American women >or=65 years of age. Incident fractures were confirmed by physician adjudication of radiology reports. There were 2532 incident nontraumatic/nonvertebral fractures during 13.6 yr of follow-up including 509 wrist and 703 hip fractures. RESULTS: Women with the C/C genotype had somewhat lower distal radius BMD compared with those with the T/T genotype (CC=0.358 g/cm(2), CT=0.361 g/cm(2), TT=0.369 g/cm(2), p=0.003). The C/C genotype was also associated with increased risk of non-spine, low traumatic fractures (HR: 1.18; 95% CI: 1.04, 1.33) and wrist fractures (HR: 1.33; 95% CI: 1.01, 1.75) compared with the T/T genotype in age-adjusted models. Further adjustments for distal radius BMD only slightly attenuated these associations. The VDR polymorphism was not associated with hip fracture. The population attributable risk (PAR) of the C/C genotype for incident fractures was 6.1%. The PAR for established risk factors for fracture were: low femoral neck BMD (PAR=16.3%), maternal history of fracture (PAR=5.1%), low body weight (PAR=5.3%), corticosteroid use (PAR=1.3%), and smoking (PAR=1.6%). Similar PAR results were observed for wrist fractures. CONCLUSIONS: The common and potentially functional VDR translation start site polymorphism confers a modestly increased relative risk of fracture among older white women. However, the high frequency of this variant confers a population attributable risk that is similar to or greater than several established risk factors for fracture. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/17280526/Association_of_the_VDR_translation_start_site_polymorphism_and_fracture_risk_in_older_women_ L2 - https://doi.org/10.1359/jbmr.070201 DB - PRIME DP - Unbound Medicine ER -