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J Hum Genet. 2006;51(2):112-7. Epub 2005 Dec 22.

Association study of semaphorin 7a (sema7a) polymorphisms with bone mineral density and fracture risk in postmenopausal Korean women.

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Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, 700-412 Daegu, Republic of Korea.


Bone mineral density (BMD), the major factor determining bone strength, is closely related to osteoporotic fracture risk and is determined largely by multiple genetic factors. Semaphorin 7a (SEMA7A), a recently described member of the semaphorin family, has been shown to play a critical role in the activation of monocyte/macrophages that share progenitors with bone-resorbing osteoclasts and thus might contribute to osteoclast development. In the present study, we directly sequenced the SEMA7A gene in 24 Korean individuals, and identified 15 sequence variants. Five polymorphisms (+15667G > A, +15775C > G, +16285C > T, +19317C > T, +22331A > G) were selected and genotyped in postmenopausal Korean women (n = 560) together with measurement of the areal BMD (g/cm2) of the anterior-posterior lumbar spine and the non-dominant proximal femur using dual-energy X-ray absorptiometry. We found that polymorphisms of the SEMA7A gene were associated with the BMD of the lumbar spine and femoral neck. SEMA7A + 15775C > G and SEMA7A+22331A > G were associated with low BMD of the femoral neck (P = 0.02) and lumbar spine (P = 0.04) in a recessive model. SEMA7A-ht4 also showed an association with risk of vertebral fracture (OR = 1.87-1.93, P = 0.02-0.03). Our results suggest that variations in SEMA7A may play a role in decreased BMD and risk of vertebral fracture.

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