Association study of semaphorin 7a (sema7a) polymorphisms with bone mineral density and fracture risk in postmenopausal Korean women.
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.
Koh
Jung-Min
JM
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.
Oh
Bermseok
B
National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, 122-701, Seoul, South Korea.
Lee
Jong Yong
JY
National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, 122-701, Seoul, South Korea.
Lee
Jong-Keuk
JK
National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, 122-701, Seoul, South Korea.
Kimm
Kuchan
K
National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Ku, 122-701, Seoul, South Korea.
Kim
Ghi Su
GS
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.
Park
Byung Lae
BL
Department of Genetic Epidemiology, SNP Genetics, 11th Floor, Maehun B/D, 13 Chongro 4 Ga, Chongro Gu, 110-834, Seoul, Republic of Korea.
Cheong
Hyun Sub
HS
Department of Genetic Epidemiology, SNP Genetics, 11th Floor, Maehun B/D, 13 Chongro 4 Ga, Chongro Gu, 110-834, Seoul, Republic of Korea.
Shin
Hyoung Doo
HD
Department of Genetic Epidemiology, SNP Genetics, 11th Floor, Maehun B/D, 13 Chongro 4 Ga, Chongro Gu, 110-834, Seoul, Republic of Korea.
Hong
Jung Min
JM
Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, 700-412, Daegu, Republic of Korea.
Kim
Tae-Ho
TH
Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, 700-412, Daegu, Republic of Korea.
Park
Eui Kyun
EK
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.
Kim
Shin-Yoon
SY
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.
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
D015703:Antigens, CD; D058851:GPI-Linked Proteins; C118753:SEMA7A protein, human; D039961:Semaphorins