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


BACKGROUND
Vitamin D-binding protein (DBP) plays a critical role in the transport and metabolism of metabolites of vitamin D, including the key calciotropic hormone 1alpha,25-dihydroxyvitamin D3 (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.


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.
School of Clinical & Laboratory Sciences, The Medical School, University of Newcastle, Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Z H
ZH
Al-oanzi
S P
SP
Tuck
S S
SS
Mastana
G D
GD
Summers
D B
DB
Cook
R M
RM
Francis
H K
HK
Datta
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D050723:Fractures, Bone / Q000097:blood / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D014809:Vitamin D-Binding Protein / Q000097:blood / Q000235:genetics*
D014809:Vitamin D-Binding Protein