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


BACKGROUND
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.


CONCLUSIONS
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.
Giampietro
P F
PF
Marshfield Clinic, Department of Medical Genetic Services, 1000 North Oak Avenue, Marshfield, WI 54449, USA. pfgiampietro@pediatrics.wisc.edu
McCarty
C
C
Mukesh
B
B
McKiernan
F
F
Wilson
D
D
Shuldiner
A
A
Liu
J
J
LeVasseur
J
J
Ivacic
L
L
Kitchner
T
T
Ghebranious
N
N
D000368:Aged; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics; D004812:Epidemiologic Methods; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D015850:Interleukin-6 / Q000235:genetics; D026502:LDL-Receptor Related Proteins / Q000235:genetics; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000502:physiology; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D014922:Wisconsin / Q000453:epidemiology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5