Osteoporosis International

, Volume 21, Issue 3, pp 467–477

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

Authors

    • Marshfield Clinic, Department of Medical Genetic Services
    • Department of PediatricsUniversity of Wisconsin-Madison
  • C. McCarty
    • Marshfield Clinic Research Foundation, Center for Human Genetics
  • B. Mukesh
    • Alcon Research Ltd.
  • F. McKiernan
    • Marshfield Clinic, Department of Rheumatology
  • D. Wilson
    • Marshfield Clinic, Department of Rheumatology
  • A. Shuldiner
    • University of Maryland School of Medicine
  • J. Liu
    • University of Maryland School of Medicine
  • J. LeVasseur
    • University of Wisconsin-Madison
    • Marshfield Clinic Research Foundation
  • L. Ivacic
    • Marshfield Clinic Research Foundation, Center for Human Genetics
  • T. Kitchner
    • Marshfield Clinic Research Foundation, Center for Human Genetics
  • N. Ghebranious
    • Marshfield Clinic Research Foundation, Center for Human Genetics
Original Article

DOI: 10.1007/s00198-009-0981-3

Cite this article as:
Giampietro, P.F., McCarty, C., Mukesh, B. et al. Osteoporos Int (2010) 21: 467. doi:10.1007/s00198-009-0981-3

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.

Keywords

CigaretteGene–environment interactionIL6LRP5OsteoporosisSmoking

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2009