Association of FLT3 Polymorphisms With Low BMD and Risk of Osteoporotic Fracture in Postmenopausal Women

Authors

  • Jung-Min Koh,

    1. Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea
    2. Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    3. These authors contributed equally to this work
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  • Bermseok Oh,

    1. These authors contributed equally to this work
    2. National Genome Research Institute, National Institute of Health, Seoul, Korea
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  • Jong-Young Lee,

    1. National Genome Research Institute, National Institute of Health, Seoul, Korea
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  • Jong-Keuk Lee,

    1. Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea
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  • Kuchan Kimm,

    1. Department of Padiatrics, Eulji University School of Medicine, Daejeon, Korea
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  • Byung Lae Park,

    1. Department of Genetic Epidemiology, SNP Genetics, Seoul, Korea
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  • Hyoung Doo Shin,

    1. Department of Genetic Epidemiology, SNP Genetics, Seoul, Korea
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  • Il-Kwon Lee,

    1. Genome Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeonnam, Korea
    2. Department of Hematology/Oncology, Chonnam National University Medical School, Gwangju, Korea
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  • Hyeoung-Joon Kim,

    1. Genome Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeonnam, Korea
    2. Department of Hematology/Oncology, Chonnam National University Medical School, Gwangju, Korea
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  • Jung-Min Hong,

    1. Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea
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  • Tae-Ho Kim,

    1. Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea
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  • Ghi Su Kim,

    1. Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea
    2. Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Shin-Yoon Kim,

    1. Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea
    2. Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University Hospital, Daegu, Korea
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  • Eui Kyun Park

    Corresponding author
    1. Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea
    2. Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, Daegu, Korea
    • Address reprint requests to: Eui Kyun Park, PhD Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, 188-1 Samduk 2-ga, Jung-gu, Daegu 700-412, Republic of Korea
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  • The authors state that they have no conflicts of interest.

Abstract

The genetic effects of FLT3 polymorphisms on BMD and fracture risk in postmenopausal women were studied. We found that FLT3+13348C>T polymorphism and haplotype 2 were significantly associated with low BMD and high risk of fracture.

Introduction: FMS-related tyrosine kinase 3 (FLT3) has been shown to play a critical role in the development of myelolymphoid progenitors and in the development of osteoclasts, but any possible genetic effect of FLT3 on bone metabolism has not been studied.

Materials and Methods: To study a possible genetic effect of FLT3, we directly sequenced the FLT3 gene in 24 Korean individuals and identified 23 sequence variants. Seven polymorphisms were selected and genotyped in Korean postmenopausal women (n = 946).

Results: We found that FLT3+13348C>T was associated with low BMD at the lumbar spine (p = 0.04) and femoral neck (p = 0.04). Haplotype analysis revealed that FLT3-ht2 (TTCTT) containing the rare allele in the +13348 position also showed significant association with low BMD in the lumbar spine (p = 0.04) and femoral neck (p = 0.05). Consistent with these results, the FLT3+13348C>T polymorphism and FLT3-ht2 were also significantly associated with high risk of fracture in the vertebrae (OR = 1.44–1.58; p = 0.03–0.04 and OR = 1.45–1.59; p = 0.02–0.03, respectively) and in any sites (OR = 1.34–1.81; p = 0.02–0.03 and OR = 1.34–1.81; p = 0.02–0.03, respectively).

Conclusions: These results suggest that FLT3 polymorphisms play a role in determination of BMD and subsequent fractures in postmenopausal women.

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