Recapitulation of the Genetic Association of PLXNA2 with Bone Density and Osteoporosis via In Vitro Experiments Using a Korean Female Cohort
Abstract
Osteoporosis is a bone disorder in which the imbalance of osteoclasts and osteoblasts leads to bone-destructive diseases especially among elderly women. Several factors, including genetic and environmental factors, contribute to the pathogenesis of these diseases. Bone mineral density
(BMD) is a robust factor that influences osteoporosis; the development of osteoporosis in the elderly is estimated based on the BMD. Our previous microarray assay using murine preosteoblast cells revealed that Plexin A2 is associated with the differentiation and mineralization of bone-forming
osteoblasts via bone morphogenetic protein 2 signaling. For our in vitro replication study using a Korean female cohort, we analyzed the genetic variation of PLEXIN A2 (PLXNA2) and its paralog genes (PLXNA1, A3, and A4) based on 125 single nucleotide polymorphisms (SNPs) associated
with bone density and osteoporosis. In this study, the PLXNA2 gene was confirmed as a robust candidate gene associated with osteoporosis in Korean women. We have demonstrated that the SNPs rs4844649 (p = 9.3×10−3) and rs3748737 (p = 2.7×10−3)
of PLXNA2 were the most significantly associated with bone density and osteoporosis, respectively. Consequently, this study demonstrates that the PLXNA2 gene is implicated in bone metabolism, further supporting the genetic association between polymorphisms in PLXNA2 and
osteoporosis. Our current findings also suggest that polymorphisms in PLXNA2 may serve as feasible clinical targets for…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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