Background: Osteoporosis is a skeletal disorder, characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to increased risk of fracture. Recently, the role of age-related pro-inflammatory cytokines, such as interleukin (IL)-1α, in stimulating bone resorption has been suggested. As osteoporosis has a strong genetic background, the aim of our study was to evaluate the association of two IL-1α gene single nucleotide polymorphisms (SNPs) rs2071375 (+12534G>A) and rs17651 (+4845G>T) with osteoporotic phenotypes as well as to find the association with IL-1α gene expression in human bone tissue.
Methods: Genotyping was performed in 671 Slovenian participants, 125 elderly men, 490 post- and 56 premenopausal women. Bone mineral density (BMD) at the lumbar spine, femoral neck and total hip were measured. Biochemical markers of bone turnover were measured in women.
Results: Significant association of GG/TA haplotype with higher femoral neck and total hip BMD in elderly men and women was shown (p=0.009 and 0.030, respectively). In men, the association of the GG/GG haplotype with higher femoral neck BMD was of limited statistical significance (p=0.050). In women, significant association of studied genetic variants with serum C-terminal crosslinking telopeptides of type I collagen and bone alkaline phosphatase were found (p=0.033 and 0.029, respectively). No influence on IL-1α expression was found. Finally, significantly lower odds ratio for hip fracture associated with the presence of TA haplotype was found (p=0.026).
Conclusions: Our results of the association of IL-1α gene single nucleotide polymorphisms (SNPs) rs2071375 (+12534G>A) and rs17651 (+4845G>T) with osteoporotic features indicate its role in pathogenesis of osteoporosis. However, these findings need further functional and clinical confirmation.