Association of PLXNA2 polymorphisms with vertebral fracture risk and bone mineral density in postmenopausal Korean population

Introduction: Plexin A2 (PLXNA2) is a receptor that recognizes secreted or membrane-bound semaphorin 3A, which is implicated in neural regulation of bone metabolism. Materials and methods: In the present study, we identified 48 genetic polymorphisms in PLXNA2 by resequencing, and 10 single nucleotide polymorphisms (SNPs) were selected for further investigation into their potential involvement in osteoporosis in a postmenopausal population (n=560). Results: Two SNPs, +14G>A (Gln5Arg) and +183429C>T (Tyr1621Tyr), and Block1-ht2 were associated with risk of vertebral fracture (p=0.01-0.05), and three SNPs, +799G>A (Ala267Thr), +135391G>A, and +190531G>C, were associated with bone mineral density at various femur sites (p=0.003-0.03). Particularly, the minor allele of +14G>A was associated with a protective effect on vertebral fracture and higher lumbar bone mineral density, suggesting that +14G>A may be a useful marker for osteoporosis and its related fracture. Conclusion: These results provide, for the first time, evidence supporting the association of PLXNA2 with osteoporosis in postmenopausal women.