Vitamin D-binding protein gene microsatellite polymorphism influences BMD and risk of fractures in men

Abstract

Summary: Here we report the results of a vitamin D-binding protein gene microsatellite polymorphism study in 170 men, comprising healthy male subjects and men with osteoporosis-related symptomatic vertebral fractures. We confirm the results of an earlier study in a different cohort, showing relationship between certain genotypes of (TAAAn)-Alu repeats and reduced BMD and vertebral fractures. Introduction: Vitamin D-binding protein (DBP) plays a critical role in the transport and metabolism of metabolites of vitamin D, including the key calciotropic hormone 1α,25-dihydroxyvitamin D 3 (1,25(OH)2D3). Methods: We have investigated intra-intronic variable tandem (TAAA)n-Alu repeat expansion in the DBP gene in 170 men, comprising healthy male subjects and men with idiopathic osteoporosis and low trauma fractures. Results and conclusions: The predominant DBP-Alu genotype in the control subjects was 10/10 (frequency 0.421), whereas the frequency of this genotype in men with osteoporosis was 0.089. DBP-Alu alleles*10,*8 and*9, respectively, were the three commonest in both healthy subjects and men with osteoporosis. Allele*10 was associated with a lower risk of osteoporosis (OR 0.39, 95% CI 0.25-0.64; p<0.0005), as was allele*11 (odds ratio 0.09, 95% CI 0.01-0.67; p<0.007). Logistic regression gave similar results, showing that individuals with genotype 10/10 and 19-20 repeats (genotypes 9/10, 9/11, 10/10,) are protected from fracture or osteoporosis. Overall, there was a relationship between DBP Alu genotype and BMD, suggesting that DBP-Alu genotype may influence fracture risk. This effect may be mediated by changes in the circulating concentrations of DBP which influences free concentrations of vitamin D. © 2007 International Osteoporosis Foundation and National Osteoporosis Foundation.