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Fok I Polymorphism at Translation Initiation Site of the Vitamin D Receptor Gene Predicts Bone Mineral Density and Vertebral Fractures in Postmenopausal Italian Women
Author(s) -
Gennari Luigi,
Becherini Lucia,
Mansani Riccardo,
Masi Laura,
Falchetti Alberto,
Morelli Annamaria,
Colli Emanuela,
Gonnelli Stefano,
Cepollaro Chiara,
Brandi Maria Luisa
Publication year - 1999
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1999.14.8.1379
Subject(s) - foki , bone mineral , medicine , calcitriol receptor , osteoporosis , endocrinology , genotype , femoral neck , bone density , allele , polymorphism (computer science) , vitamin d and neurology , genetics , biology , gene
A novel T/C polymorphism (ATG to ACG) at the translation initiation site of the vitamin D receptor (VDR) gene, defined by Fok I restriction endonuclease, has been recently associated with variation in bone mineral density (BMD) and rates of bone loss in a group of postmenopausal Mexican‐American women. The presence of the restriction site, designated as f, allows protein translation to initiate from the first ATG, while the allele lacking the site, indicated as F, initiates translation at a second ATG. In this study, we investigated the role of Fok I polymorphism in a group of 400 postmenopausal women of Italian descent stratified for BMD into osteoporotic ( n = 164), osteopenic ( n = 117), and normal ( n = 119) groups. There were 159 (41%) FF homozygotes, 55 (14%) ff homozygotes, and 186 (45%) Ff heterozygotes. In the whole population, we observed a weak association between Fok I polymorphism and lumbar BMD ( p = 0.06, analysis of covariance [ANCOVA]) but not with femoral neck BMD ( p = 0.5, ANCOVA). Interestingly, the effect of Fok I genotypes on lumbar BMD was influenced by the years since menopause such that differences in BMD related to different VDR allelic variants were greater among women in the first 5 years of menopause ( p = 0.04, ANCOVA), progressively declining afterward. In addition, a significantly higher prevalence of ff genotype in osteoporotic than in osteopenic and normal women was observed ( p = 0.04, Chi‐square test). Finally, ff genotype resulted significantly over‐represented in the group of women with a vertebral fracture as compared with controls ( p = 0.003, Chi‐square test), equivalent to a relative risk of 2.58 (95% confidence intervals 1.36–4.91). We conclude that in this population, Fok I polymorphism at the VDR gene locus accounts for a part of the heritable component of BMD at the lumbar spine.