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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.

AbstractSUMMARY:
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.
AuthorsP F Giampietro, C McCarty, B Mukesh, F McKiernan, D Wilson, A Shuldiner, J Liu, J LeVasseur, L Ivacic, T Kitchner, N Ghebranious
JournalOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA (Osteoporos Int) Vol. 21 Issue 3 Pg. 467-77 (Mar 2010) ISSN: 1433-2965 [Electronic] England
PMID19506792 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-6
  • LDL-Receptor Related Proteins
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
Topics
  • Aged
  • Body Mass Index
  • Bone Density (genetics)
  • Epidemiologic Methods
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects)
  • Interleukin-6 (genetics)
  • LDL-Receptor Related Proteins (genetics)
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Middle Aged
  • Osteoporosis, Postmenopausal (epidemiology, etiology, genetics)
  • Polymorphism, Single Nucleotide
  • Postmenopause (physiology)
  • Smoking (adverse effects, epidemiology)
  • Wisconsin (epidemiology)

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