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Significant Association between Common Polymorphisms in the Aromatase Gene CYP19A1 and Bone Mineral Density in Postmenopausal Women

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Abstract

17β-Estradiol is important in maintaining bone structure, and regulation of its synthesis plays an important role in the development of postmenopausal osteoporosis. We and others have demonstrated associations between variation in the CYP19A1 gene (encoding aromatase) and areal bone mineral density (aBMD) phenotypes in women. In the present study 33 tag polymorphisms were genotyped across the CYP19A1 gene in a population of 1,185 Caucasian postmenopausal women to test the association between sequence variations, total DXA hip aBMD, and circulating 17β-estradiol levels. An in silico bioinformatics analysis was performed for single nucleotide polymorphisms (SNPs) associated with aBMD to identify putative functional effects, while linkage disequilibrium analysis of these SNPs was undertaken with previously published sequence variants. Five SNPs located in the central third of the gene were strongly associated with total-hip aBMD after adjustment for age (P = 0.006–0.013). A haplotype analysis of these five SNPs revealed an association between the haplotype C-G-G-G-C and increased aBMD (P = 0.008) and the haplotype A-A-A-A-A and a decreased aBMD (P = 0.021). The haplotype frequency was 9.0% for C-G-G-G-C and 15.4% for A-A-A-A-A, with the variation in mean total-hip aBMD explained by the haplotype analyses being 5% and 7%, respectively. None of these polymorphisms was significantly associated with circulating 17β-estradiol levels. In conclusion, common genetic variations within the CYP19A1 gene are significantly associated with aBMD in postmenopausal Caucasian women.

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Acknowledgement

We thank the staff of the Western Australian Bone and Cartilage group who contributed to patient recruitment, genotyping, and data analysis.

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Authors and Affiliations

  1. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia

    B. H. Mullin, J. R. Lewis, S. G. Wilson & R. L. Prince

  2. School of Biomedical Sciences, Curtin University of Technology, Bentley, WA, Australia

    B. H. Mullin

  3. Telethon Institute for Child Health Research, UWA Centre for Child Health Research, University of Western Australia, Nedlands, WA, Australia

    K. W. Carter

  4. School of Medicine and Pharmacology, University of Western Australia, Nedlands, Perth, WA 6009, Australia

    J. R. Lewis, S. G. Wilson & R. L. Prince

  5. Cell Signalling Group, Laboratory for Cancer Medicine, Western Australia Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, WA, Australia

    E. Ingley

  6. Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK

    S. G. Wilson

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  1. B. H. Mullin
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  2. K. W. Carter
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  3. J. R. Lewis
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  4. E. Ingley
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  5. S. G. Wilson
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  6. R. L. Prince
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Corresponding author

Correspondence to J. R. Lewis.

Additional information

B. H. Mullin and K. W. Carter contributed equally to this study.

The authors have stated that they have no conflict of interest.

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Mullin, B.H., Carter, K.W., Lewis, J.R. et al. Significant Association between Common Polymorphisms in the Aromatase Gene CYP19A1 and Bone Mineral Density in Postmenopausal Women. Calcif Tissue Int 89, 464–471 (2011). https://doi.org/10.1007/s00223-011-9535-8

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  • DOI: https://doi.org/10.1007/s00223-011-9535-8

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