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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Authors | P F Giampietro, C McCarty, B Mukesh, F McKiernan, D Wilson, A Shuldiner, J Liu, J LeVasseur, L Ivacic, T Kitchner, N Ghebranious |
Journal | Osteoporosis 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 |
PMID | 19506792
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Interleukin-6
- LDL-Receptor Related Proteins
- LRP5 protein, human
- Low Density Lipoprotein Receptor-Related Protein-5
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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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