The presence of a polymorphism at the translation initiation site of the vitamin D receptor gene is associated with low bone mineral density in postmenopausal mexican-American women

✍ Scribed by Coleman Gross; T. Ross Eccleshall; Peter J. Malloy; Marie Luz Villa; Robert Marcus; David Feldman

• Publisher: American Society for Bone and Mineral Research
• Year: 2010
• Tongue: English
• Weight: 531 KB
• Volume: 11
• Category: Article
• ISSN: 0884-0431
• DOI: 10.1002/jbmr.5650111204

✦ Synopsis

We examined the association of bone mineral density (BMD) with a polymorphism in the gene encoding the vitamin D receptor (VOR) that causes a change in the predicted protein sequence. The polymorphism results from a C-to-T transition and creates an initiation codon (ATG) three codons proximal to a downstream start site. The polymorphism can be defined by a restriction fragment length polymorphism (RFLP) using the restriction endonuclease FokI. The presence of a Fokl site, designated f, allows protein translation to initiate from the first ATG. The allele lacking the site (designated F), initiates from a second ATG site. Thus, translation products from these alleles are predicted to differ by three amino acids with the f variant elongated. In a group of 100 postmenopausal Mexican-American Caucasian women, subjects with the Ifgenotype (15%of the study population) had a 12.8% lower BMO at the lumbar spine than FF subjects (37% of the population) (p =0.01). Heterozygote (Ft) subjects (48%of the population) had an intermediate BMD. This association between BMD and genotype was not apparent at the femoral neck or forearm. Over a 2-year follow-up period, a decrease in BMD at the femoral neck was greater in If compared with FF subjects (-4.7% vs, -0.5%, P =0.005). This trend was not apparent at the lumbar spine or forearm. There were no differences between genotype groups in measurements of 25hydroxyvitamin D (25(OH)D), calcitriol, parathyroid hormone (11'111), osteocalcin, or urinary pyridinolines. We conclude that the Fokl polymorphism of the VDR gene correlates significantly with decreased BMO at the lumbar spine and with an increased rate of bone loss at the hip in If subjects. We emphasize that these initial data should be interpreted with caution but that the utility of this polymorphism as a genetic marker to determine BMO and osteoporosis risk warrants further study in larger populations with subjects of diverse ethnic backgrounds. (J Bone