title: Association study of semaphorin 7a (sema7a) polymorphisms with bone mineral density and fracture risk in postmenopausal Korean women.
abstract: 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.
authors.affiliation: Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, 700-412, Daegu, Republic of Korea.|Division of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, 138-736, Seoul, Republic of Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Koh
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, 122-701, Seoul, South Korea.
authors.forename: Bermseok
authors.initials: B
authors.lastname: Oh
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, 122-701, Seoul, South Korea.
authors.forename: Jong Yong
authors.initials: JY
authors.lastname: Lee
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, 122-701, Seoul, South Korea.
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
authors.affiliation: National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, 122-701, Seoul, South Korea.
authors.forename: Kuchan
authors.initials: K
authors.lastname: Kimm
authors.affiliation: Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, 700-412, Daegu, Republic of Korea.|Division of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, 138-736, Seoul, Republic of Korea.
authors.forename: Ghi Su
authors.initials: GS
authors.lastname: Kim
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, 11th Floor, Maehun B/D, 13 Chongro 4 Ga, Chongro Gu, 110-834, Seoul, Republic of Korea.
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, 11th Floor, Maehun B/D, 13 Chongro 4 Ga, Chongro Gu, 110-834, Seoul, Republic of Korea.
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, 11th Floor, Maehun B/D, 13 Chongro 4 Ga, Chongro Gu, 110-834, Seoul, Republic of Korea.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.affiliation: Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, 700-412, Daegu, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Hong
authors.affiliation: Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, 700-412, Daegu, Republic of Korea.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, 700-412, Daegu, Republic of Korea. epark@knu.ac.kr.
authors.forename: Eui Kyun
authors.initials: EK
authors.lastname: Park
authors.affiliation: Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, 700-412, Daegu, Republic of Korea.|Department of Orthopedic Surgery, Kyungpook National University School of Medicine, 50 Samduk 2-ga, Jung-gu, 700-712, Daegu, Republic of Korea.
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D015502:Absorptiometry, Photon; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D015519:Bone Density / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D005270:Femur Head / Q000737:chemistry; D050723:Fractures, Bone / Q000235:genetics*; D058851:GPI-Linked Proteins; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007723:Korea; D008159:Lumbar Vertebrae / Q000737:chemistry; D008875:Middle Aged; D008969:Molecular Sequence Data; D015663:Osteoporosis, Postmenopausal / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D039961:Semaphorins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; C118753:SEMA7A protein, human; D039961:Semaphorins