Association of transforming growth factor beta1 genotype with spinal osteophytosis in Japanese women

To examine the possible relationship between a T-->C polymorphism at nucleotide position 29 of the transforming growth factor beta1 (TGFbeta1) gene and genetic susceptibility to radiographic spinal osteophytosis.

A total of 540 postmenopausal Japanese women were subjected to radiography of the spine and determination of bone mineral density (BMD) for the lumbar spine and total body. Changes in lumbar intervertebral discs were examined in 67 individuals with either osteoporosis or spinal osteophytosis by magnetic resonance imaging (MRI). TGFbeta1 genotype was determined with an allele-specific polymerase chain reaction assay. The serum concentration of TGFbeta1 was measured in 29 control subjects and in 36 patients with spinal osteophytosis.

Among all study subjects, the prevalence of radiographic spinal osteophytosis in individuals with the CC genotype was greater than that in those with the TC or TT genotype. Logistic regression analysis, adjusted for age, height, body weight, time since menopause, smoking status, body fat, lean mass, and either lumbar spine or total body BMD, demonstrated that the frequency of the C allele in subjects with spinal osteophytosis was significantly greater than that in those without this condition. Comparison among control, osteoporosis, and spinal osteophytosis groups also revealed that the C allele was more prevalent in subjects with osteophytosis than in controls, even after adjustment for BMD. In contrast, as previously shown, the frequency of the C allele was lower in osteoporosis patients than in controls. The intervertebral disc area and the ratio of disc area to vertebral body area, as determined by MRI, were also lowest in subjects with the CC genotype. The serum concentration of TGFbeta1 increased with the number of C alleles in both controls and patients with spinal osteophytosis.

The T29-->C polymorphism of the TGFbeta1 gene exhibited inverse patterns of association with genetic susceptibility to spinal osteophytosis and with osteoporosis. Although radiographic evaluation of osteophytes might not reflect the actual disease severity, the C allele, which protects against osteoporosis, may be a risk factor for genetic susceptibility to spinal osteophytosis.