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The role of cigarette smoking and statins in the development of postmenopausal osteoporosis: a pilot study utilizing the Marshfield Clinic Personalized Medicine Cohort

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Abstract

Summary

A cohort of postmenopausal osteoporotic females and controls with normal bone mineral density, the interleukin 6 (IL6) −634G > C (rs1800796) C allele of the promoter region showed association with osteoporosis. The lipoprotein receptor-related protein 5 (LRP5) gene showed association between C135242T C/T alleles and osteoporosis only in smokers, suggesting a role for environmental interaction.

Introduction

A nested case–control study within a population-based cohort was undertaken to assess the relative impact of cigarette smoking, statin use, genetic polymorphisms, and one-way interaction of these factors on development of osteoporosis in postmenopausal women.

Methods

Genotyping of 14 single-nucleotide polymorphisms (SNPs) corresponding to vitamin D receptor gene, estrogen receptor 1, collagen type 1 alpha 1, IL6, transcription growth factor beta, apolipoprotein E, and LRP5 genes was performed in cases (n = 309) with osteoporosis and controls (n = 293) with normal bone mineral density drawn from a homogeneous Caucasian population. SNPs were chosen based on known functional consequences or prior evidence for association and genotyped using matrix-assisted laser desorption ionization time-of-flight technology.

Results

Cases differed from controls relative to body mass index, age, and smoking but not statin use. After adjusting for age, the IL6 −634G > C (rs1800796) allele showed association with osteoporosis (odds ratio (OR) for CC + CG = 2.51, p = 0.0047)), independent of statin use or smoking status. On stratification for smoking, association with LRP5 C135242T (rs545382) and osteoporosis emerged (OR 2.8 in smokers for CT alleles, p = 0.03)), suggestive of potential environmental interaction.

Conclusion

Evidence suggested a role for genetic variation in IL6 and LRP5 in conferring risk for osteoporosis in Caucasian women, with the latter manifest only in smokers.

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Acknowledgements

The authors thank Adeline Kaam for her assistance with phenotyping and Ingrid Glurich, Alice Stargardt, and Marie Fleisner, Marshfield Clinic Research Foundation, Office of Scientific Writing, for their editorial assistance in the preparation of this manuscript.

Funding

Marshfield Clinic Research Foundation; Donors to Personalized Medicine and Rheumatology

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Marshfield Clinic, Department of Medical Genetic Services, 1000 North Oak Avenue, Marshfield, WI, 54449, USA

    P. F. Giampietro

  2. Marshfield Clinic Research Foundation, Center for Human Genetics, Marshfield, WI, USA

    C. McCarty, L. Ivacic, T. Kitchner & N. Ghebranious

  3. Alcon Research Ltd., Fort Worth, TX, USA

    B. Mukesh

  4. Marshfield Clinic, Department of Rheumatology, Marshfield, WI, USA

    F. McKiernan & D. Wilson

  5. University of Maryland School of Medicine, Baltimore, MD, USA

    A. Shuldiner & J. Liu

  6. University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI, USA

    J. LeVasseur

  7. Marshfield Clinic Research Foundation, Marshfield, WI, USA

    J. LeVasseur

  8. Department of Pediatrics, University of Wisconsin-Madison, Waisman Center 351, 1500 Highland Avenue, Madison, WI, 53705-9345, USA

    P. F. Giampietro

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  1. P. F. Giampietro
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  2. C. McCarty
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Correspondence to P. F. Giampietro.

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Giampietro, P.F., McCarty, C., Mukesh, B. et al. The role of cigarette smoking and statins in the development of postmenopausal osteoporosis: a pilot study utilizing the Marshfield Clinic Personalized Medicine Cohort. Osteoporos Int 21, 467–477 (2010). https://doi.org/10.1007/s00198-009-0981-3

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