Association of Common Vitamin D Receptor Gene Variations with Fracture Risk and Bone Mineral Density in Postmenopausal Korean Population.

Hwang,  Joo Yeon; Lee,  Seung Hun; Kim,  Ghi Su; Koh,  Jung Min; Go,  Min Jin; Kim,  Tae Ho; Hong,  Jung Min; Park,  Eui Kyun; Kim,  Shin Yoon; Lee,  Jong Young

doi:2009.7.1.13

Genomics Inform > Volume 7(1); 2009 > Article

Original Article

Genomics & Informatics 2009;7(1): 13-19.

DOI: https://doi.org/10.5808/gi.2009.7.1.013

Association of Common Vitamin D Receptor Gene Variations with Fracture Risk and Bone Mineral Density in Postmenopausal Korean Population.

Joo Yeon Hwang, Seung Hun Lee, Ghi Su Kim, Jung Min Koh, Min Jin Go, Tae Ho Kim, Jung Min Hong, Eui Kyun Park, Shin Yoon Kim, Jong Young Lee

¹The Center for Genome Science, National Institute of Health, Seoul, Korea. syukim@wmail.knu.ac.kr
²Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea.
³Deparement of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, Daegu, Korea.
⁴Division of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
⁵Deparement of Orthopedic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea.

Abstract

Osteoporosis is characterized by impaired osteogenesis. BMD is a major determinant of bone strength. The role of the VDR gene in predisposition to primary osteoporosis has been recognized. However, population-based case-control studies have been reported controversial results for known candidate genes in an ethnically distinct group. To determine the genetic effects of VDR variants on osteoporosis and BMD, we directly sequenced the VDR gene in 24 unrelated Korean individuals and identified eighteen sequence variants. We investigated the potential involvement of eight SNPs in osteoporosis in postmenopausal women (n = 729). Two SNPs (LD) in intron 2, -5294G > C (rs2238135) and -4817G > A (rs17882443) showed the evidence of association with enhanced BMD of the femoral neck (p(additive) =0.031 for rs2238135; p(additive)=0.017 and p(dominant)= 0.019 for 17882443). Moreover, VDR -4817G > A was significantly associated with protective effect on all fracture risk (p(recessive)=0.035, OR=0.2, 95% CI=0.05~0.89), and tended to be higher BMD values at various proximal femur sites. Therefore, we suggest that the -4817G > A may be useful genetic marker for vitamin D-related metabolism and may have an important role in the increased BMD of the proximal femur in postmenopausal Korean women.

Keywords: BMD; fracture; osteoporosis; polymorphism,VDR