Genetic Association Study of Osteoporotic Vertebral Compression Fractures in Postmenopausal Women

Abstract

Vascular endothelial growth factor (VEGF) is involved in bone formation through its role in angiogenesis. VEGF is also known to promote the healing of fractures and hyperhomocysteinemia is associated with the risk of skeletal health problems, such as osteoporosis, low body mineral density, and fracture. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are involved in homocysteine metabolism. Thus, we determined whether or not VEGF, MTHFR, and TS polymorphisms are associated with osteoporotic vertebral compression fractures in postmenopausal Korean women. The study subjects consisted of 82 patients with osteoporotic vertebral compression fractures and 117 control postmenopausal Korean women. PCR-RFLP and real-time PCR assay were used to analyze VEGF, MTHFR, and TS polymorphisms. Homocysteine levels were also measured to determine whether or not polymorphisms of the VEGF gene affect homocysteine/folate metabolism. The AA genotype of the -2578C>A polymorphism were significantly different between the stroke and control groups; no significant differences in the -1154G>A, -634G>C, and 936C>T genotype frequencies existed. However, the A-G-G-C haplotype had a tendency to be associated with osteoporotic vertebral compression fractures in postmenopausal Korean women. Associations between the VEGF -2578C>A polymorphism and homocysteine levels were also noted. There was not significant association of MTHFR and TS polymorphisms with osteoporotic vertebral compression fractures. In summary, these results suggest that the VEGF -2578C>A polymorphisms and VEGF haplotypes may play an important role in the etiology of osteoporotic vertebral compression fractures in postmenopausal Korean women.