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Variation in the PTH2R gene is associated with age-related degenerative changes in the lumbar spine

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Abstract

In the elderly, degenerative changes in the lumbar spine are common, contributing to falsely elevated bone mineral density (BMD) values. The parathyroid hormone (PTH) system plays an important role in the regulation of bone turnover and we explore the hypothesis that polymorphisms (SNPs) within genes in this pathway (PTH, PTHLH, PTH1R and PTH2R) contribute to degenerative manifestations of the spine in elderly women. The study included 1,004 Swedish women aged 75 years from the population-based OPRA cohort who attended follow-up at 5 and 10 years. Lumbar spine BMD was assessed by dual energy X-ray absorptiometry (DXA) and each individual vertebra was evaluated visually on the DXA image for apparent degenerative manifestations. Six SNPs in PTH and 3 SNPs each in PTH1R, PTH2R and PTHLH were analysed. Among women with degenerative manifestations at the lumbar spine, there was an over-representation at baseline of those carrying the PTH2R SNP rs897083 A-allele (p = 0.0021; odds ratio 1.5 95 % CI 1.2–2.0) and across the duration of follow-up (p = 0.0008). No association was observed between degenerative manifestations and variation in the other genes. None of the PTH hormone system genes were associated with vertebral fracture. Variation in the PTH2R gene (Chr2q34, rs897083) may contribute to the age-associated degenerative manifestations that develop at the lumbar spine.

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Acknowledgments

Thanks are extended to Åsa Almgren, Siv Braun and Lisa Quensel for data management, Jan-Åke Nilsson for statistical advice, Lisa Jansson for genotyping, Dr Anna-Karin Abelson and Dr Gaurav Garg for assistance with manuscript preparation and proof reading, the research nurses at the Clinical and Molecular Osteoporosis Research Unit and all the women who kindly participated in the study. Financial support for the study was received from the Swedish Research Council (Grant K2009-53X-14691-07-3), Greta and Johan Kock Foundation, A Påhlsson Foundation, A Österlund Foundation, Herman Järnhardt Foundation, King Gustav V and Queen Victoria Fundation, Malmö University Hospital Research Foundation, Research and Development Council of Region Skåne, Sweden and the Swedish Medical Society.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmö, Lund University, SE 205 02, Malmö, Sweden

    Kristina Åkesson, Max Tenne & Fiona E. McGuigan

  2. Department of Orthopaedics Malmö, Skåne University Hospital, SE 205 02, Malmö, Sweden

    Kristina Åkesson, Max Tenne & Fiona E. McGuigan

  3. Department of Orthopaedics, Karolinska University Hospital, Stockholm, Sweden

    Paul Gerdhem

  4. Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden

    Paul Gerdhem

  5. Medical Genetics Unit, Department of Clinical Sciences Malmö, Lund University, SE 205 02, Malmö, Sweden

    Holger Luthman

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  1. Kristina Åkesson
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  2. Max Tenne
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  3. Paul Gerdhem
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  4. Holger Luthman
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  5. Fiona E. McGuigan
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Correspondence to Fiona E. McGuigan.

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Åkesson, K., Tenne, M., Gerdhem, P. et al. Variation in the PTH2R gene is associated with age-related degenerative changes in the lumbar spine. J Bone Miner Metab 33, 9–15 (2015). https://doi.org/10.1007/s00774-013-0550-x

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  • DOI: https://doi.org/10.1007/s00774-013-0550-x

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