Association of the VDR translation start site polymorphism and fracture risk in older women

作者：Moffett Susan P^*; Zmuda Joseph M; Cauley Jane A; Ensrud Kristine E; Hillier Teresa A; Hochberg Marc C; Li Jia; Cayabyab Shelia; Lee Jocelyn M; Peltz Gary; Cummings Steven R

来源：Journal of Bone and Mineral Research, 2007, 22(5): 730-736.

DOI：10.1359/JBMR.070201

• vitamin D receptor
• polymorphism
• fracture
• BMD
• population attributable risk

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; >= 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 = 13%), 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.

• 出版日期2007-5