Possible involvement of vitamin D receptor gene polymorphism in male patients with ossification of spinal ligaments.
Ossification of spinal ligaments (OSL) is a common form of myelopathy characterized by heterotopic bone formation in the spinal ligaments, predominantly in men. Although the etiology of OSL is not fully understood, previous studies have strongly suggested the involvement of genetic factors in this disease. To investigate the possible involvement of vitamin D receptor (VDR) gene polymorphism in Japanese male patients with OSL, we analyzed: (a) the VDR genotype defined by BsmI polymorphism in patients with obvious OSL and controls; and (b) the effect of 1,25-dihydroxyvitamin D3 on alkaline phosphatase (ALP) activity of spinal ligament cells derived from patients without OSL. With regard to the VDR genotype, of the patients with OSL (n = 27), none had the BB genotype (0%), one had the Bb genotype (4%), and 26 had the bb genotype (96%). In the control group (n = 97) three had the BB genotype (3%), 18 had the Bb genotype (19%), and 76 had the bb genotype (78%). As a result, the B allele frequency in patients with OSL (2%) was significantly lower than in controls (12%). 1,25-Dihydroxyvitamin D3, at concentrations of 10-9 and 10-8 M, significantly increased ALP activity of the ligament cells (n = 8), suggesting that 1,25-dihydroxyvitamin D3 is able to promote osteogenic differentiation of normal ligament cells. Among the Japanese, sensitivity to vitamin D has been reported to vary between the alleles of the VDR; i.e., bone mineral density (BMD) in patients without the B allele is increased by vitamin D treatment, whereas patients with the B allele do not show such an increase in BMD. The present investigation is a small preliminary study, but the findings suggest, for the first time, that the B allele of the VDR acts as an inhibitor in the pathogenesis of human male OSL.
Shiigi
E
E
Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube 755-8505, Japan.
Sugiyama
T
T
Tanaka
H
H
Murata
H
H
Shirakura
Y
Y
Kawai
S
S
D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D008875:Middle Aged; D017887:Ossification of Posterior Longitudinal Ligament / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*
D018167:Receptors, Calcitriol; D015650:24,25-Dihydroxyvitamin D 3; D000469:Alkaline Phosphatase