Interleukin-6 promoter polymorphism is associated with bone quality assessed by calcaneus ultrasound and previous fractures in a cohort of 75-year-old women.
Interleukin 6 (IL-6) is a multifunctional cytokine and a potent stimulator of bone resorption and has been implicated in the pathogenesis of osteoporosis in postmenopausal women. The aim of this study was to investigate if a functional IL-6 promoter polymorphism (-174) was related to bone mass and fractures in a cohort consisting of 964 postmenopausal Caucasian women aged 75 years. Bone mineral density (BMD; g/cm2) of the femoral neck, lumbar spine and total body was measured using dual energy X-ray absorptiometry (DXA). Quantitative ultrasound (QUS) was also measured in the calcaneus and quantified as speed of sound (SOS; m/s), broadband ultrasound attenuation (BUA; dB/MHz), and stiffness index (SI). IL-6 genotypes was determined by restriction fragment length polymorphism (RFLP) using the restriction enzyme NlaIII. The frequencies of the different IL-6 genotypes were 27.5% (GG), 47.9% (GC), 24.6% (CC). The IL-6 polymorphism (presence of G) was independently related to a lower stiffness (beta=-0.07; P=0.03) and BUA (beta=-0.08; P=0.02), but not to BMD at any site measured by DXA. In the cohort, 420 subjects (44%) reported at least one fracture during their lifetime, and 349 (36%) reported at least one fracture after the age of 50. Using binary logistic regression, the IL-6 polymorphism (presence of G) was significantly related to an increased risk of a previous fracture during life (odds ratio 1.46, 95% CI 1.08-1.97) and to an increased risk of a fracture occurring after 50 years of age (odds ratio 1.37, 95% CI 1.004-1.88). The risk was further increased for fractures grouped as osteoporotic fractures (odds ratio 1.67, 95% CI 1.14-2.45), including forearm fractures (odds ratio 1.59, 95% CI 1.05-2.40). In conclusion, presence of G allele in the IL-6 promoter polymorphism at position -174 is independently related to previous fractures in postmenopausal women. This association may be related primarily to an altered bone quality identified by QUS and not a lower bone mass. This is also the first demonstration of association of IL-6 gene polymorphism to calcaneal QUS.
Sports Medicine, Department of Surgical and Perioperative Sciences, Umeå University Hospital, 901 85, Umeå, Sweden. anna.nordstrom@idrott.umu.se
Anna
A
Nordström
Paul
P
Gerdhem
Helena
H
Brändström
Fredrik
F
Stiger
Ulf H
UH
Lerner
Mattias
M
Lorentzon
Karl
K
Obrant
Peter
P
Nordström
Kristina
K
Akesson
D000368:Aged; D000483:Alleles; D015519:Bone Density / Q000235:genetics*; D002111:Calcaneus / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D005260:Female; D050723:Fractures, Bone / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D015663:Osteoporosis, Postmenopausal / Q000235:genetics / Q000503:physiopathology; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D014463:Ultrasonography
D015850:Interleukin-6