Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Clin Chem Lab Med. 2012 Feb 2;50(8):1379-85. doi: 10.1515/cclm-2011-0589.
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.
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.
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).
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.
骨质疏松症是一种骨骼疾病，其特征是骨量低和骨组织微结构恶化，导致骨折风险增加。最近，年龄相关的促炎细胞因子（如白细胞介素-1α）刺激骨吸收的作用已被提出。由于骨质疏松症具有很强的遗传背景，我们的研究目的是评估白细胞介素-1α基因的两个单核苷酸多态性（SNP）rs2071375（+12534G>A）和 rs17651（+4845G>T）与骨质疏松表型的关联，并找到与人类骨组织中白细胞介素-1α基因表达的关联。
在 671 名斯洛文尼亚参与者中进行基因分型，其中包括 125 名老年男性、490 名绝经后和 56 名绝经前女性。测量腰椎、股骨颈和全髋关节的骨密度（BMD）。测量女性的骨转换生化标志物。
显示 GG/TA 单倍型与老年男性和女性股骨颈和全髋关节 BMD 较高显著相关（p=0.009 和 0.030）。在男性中，GG/GG 单倍型与股骨颈 BMD 较高的关联具有有限的统计学意义（p=0.050）。在女性中，研究的遗传变异与血清 I 型胶原 C 端交联端肽和骨碱性磷酸酶显著相关（p=0.033 和 0.029）。未发现对白细胞介素-1α表达的影响。最后，发现 TA 单倍型与髋部骨折的发生几率较低相关（p=0.026）。
我们对白细胞介素-1α基因单核苷酸多态性（SNP）rs2071375（+12534G>A）和 rs17651（+4845G>T）与骨质疏松特征的关联研究结果表明，其在骨质疏松症发病机制中发挥作用。然而，这些发现需要进一步的功能和临床验证。
