Association of the OSCAR promoter polymorphism with BMD in postmenopausal women.
In an effort to identify genetic polymorphisms in potential candidate genes for osteoporosis, 10 variants were identified in the OSCAR gene using direct DNA sequencing, and 560 postmenopausal women were genotyped at five SNP loci, using the TaqMan method. The rare allele (G allele) of OSCAR-2322A>G (SNP in the 5' flanking region) showed significant association with lower BMD at various bone sites in postmenopausal women (n = 560).


BACKGROUND
BMD is the major factor for determining bone strength and osteoporotic fracture risk and is determined by both environmental and multiple genetic factors. The osteoclast-associated receptor (OSCAR) plays a critical role in osteoclast differentiation and thus is an important candidate gene for the modulation of BMD.


METHODS
Through direct sequencing in 24 Korean individuals, 10 sequence variants were identified: 2 in the 5' flanking region, 7 in the exons (including 6 nonsynonymous single-nucleotide polymorphisms [SNPs]), and 1 in an intron. Five of these polymorphisms were selected for larger-scale genotyping in postmenopausal women (n = 560). Areal BMD (g/cm2) of the anterior-posterior lumbar spine and the nondominant proximal femur was measured using DXA (Lunar Expert XL and Hologic QDR 4500-A). Lateral thoracolumbar radiographs were obtained in all subjects.


RESULTS
Using multiple regression analysis and controlling for age, years since menopause, height, weight, and evaluation machine as covariates, the rare allele (G allele) of OSCAR-2322A>G showed significant association with lower BMD at various bone sites in postmenopausal women.


CONCLUSIONS
These findings suggest that the promoter variant in OSCAR gene (OSCAR-2322A>G) might be one of genetic determinants of BMD in postmenopausal women.
Kim
Ghi Su
GS
Division of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Koh
Jung-Min
JM
Chang
Jae Suk
JS
Park
Byung Lae
BL
Kim
Lyoung Hyo
LH
Park
Eui Kyun
EK
Kim
Shin-Yoon
SY
Shin
Hyoung Doo
HD
D015502:Absorptiometry, Photon; D000367:Age Factors; D000368:Aged; D000483:Alleles; D044466:Asian People; D001827:Body Height; D001835:Body Weight; D015519:Bone Density / Q000235:genetics*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D013904:Thoracic Vertebrae / Q000000981:diagnostic imaging
D005819:Genetic Markers; C512828:OSCAR protein, human; D011956:Receptors, Cell Surface