The Effect of Interleukin-1α Polymorphisms on Bone Mineral Density and the Risk of Vertebral Fractures
The Effect of Interleukin-1α Polymorphisms on Bone Mineral Density and the Risk of Vertebral Fractures
复制标题
DOI：
10.1007/s00223-006-0059-6
复制
发表时间：
2007-01
影响因子：
4.2
通讯作者：
S. Knudsen;T. Harsløf;L. Husted;M. Carstens;L. Stenkjær;B. Langdahl
中科院分区：
文献类型：
--
作者：
S. Knudsen;T. Harsløf;L. Husted;M. Carstens;L. Stenkjær;B. Langdahl
白细胞介素-1α (IL-1α)通过破骨细胞刺激骨吸收。骨质疏松症患者的单核细胞显示IL-1α产生增加，与正常绝经后妇女相比，骨质疏松症患者的骨活检中更常检测到IL-1α mRNA。IL-1α基因存在多态性；然而，这些都没有被研究过对白种人骨骼表型的影响。我们研究了IL-1α基因多态性是否影响骨质疏松性骨折的风险、骨密度（BMD）和骨转换在462名骨质疏松患者和336名正常对照。基于先前对该基因多态性的研究和来自国际Hap-Map项目的数据，为了研究IL-1α基因中已知多态性的影响，需要检查4个多态性。采用Taqman和限制性片段长度多态性分析对C−1202-T（rs1800794）、C - 889- t （rs1800587）、T155 + 209-C（rs2071373）、C155 + 320-T（rs2856838）和G398-T（rs17561）进行了检测。采用双能x线骨密度仪检测骨密度。采用血清骨钙素、血清I型前胶原羧基末端前肽、血清骨特异性碱性磷酸酶、血清I型胶原羧基末端末端肽和尿羟脯氨酸/肌酐评价骨转换。基因型分布符合Hardy-Weinberg平衡。所有多态性均处于强连锁不平衡状态。C155 + 320-T多态性等位基因在椎体骨折患者（P= 0.06）和BMD T评分< -2.5的患者中更为常见（P= 0.05）。此外，单倍型1与BMD T评分< -2.5的风险降低相关（P= 0.02）。其他多态性或单倍型均与骨折风险或BMD T评分< -2.5无关。骨密度和骨转换与任何遗传变异都无关。总之，IL-1α基因内的所有多态性都处于强烈的连锁不平衡状态，与骨折风险、骨密度或骨转换没有令人信服的关联。
Interleukin-1α (IL-1α) stimulates bone resorption via osteoclasts. Mononuclear cells from patients with osteoporosis show increased IL-1α production, and IL-1α mRNA is more often detected in bone biopsies from osteoporotic compared to normal postmenopausal women. Polymorphisms have been identified in the IL-1α gene; however, none of these has been examined for an effect on bone phenotypes in Caucasians. We investigated if the polymorphisms in the IL-1α gene affect the risk of osteoporotic fractures, bone mineral density (BMD), and bone turnover in 462 osteoporotic patients and 336 normal controls. Based on previous studies of polymorphisms in the gene and data from the International Hap-Map Project, four polymorphisms needed examination in order to investigate the effect of known polymorphisms in the IL-1α gene. We examined C−1202-T(rs1800794), C–889-T(rs1800587), T155 + 209-C(rs2071373), C155 + 320-T(rs2856838), and G398-T(rs 17561) by Taqman and restriction fragment-length polymorphism assays. BMD was examined by dual-energy X-ray absorptiometry. Bone turnover was evaluated by serum osteocalcin, serum carboxy-terminal propeptide of human type I procollagen, serum bone-specific alkaline phosphatase, serum carboxy-terminal telopeptide of type I collagen, and urinary hydroxyproline/creatinine. Genotype distributions were in Hardy-Weinberg equilibrium. All polymorphisms were in strong linkage disequilibrium. TheCallele of the C155 + 320-T polymorphism tended to be more common among patients with vertebral fractures (P= 0.06) and patients with BMD T score <–2.5 (P= 0.05). Furthermore, haplotype 1 was associated with reduced risk of having BMD T score <–2.5 (P= 0.02). None of the other polymorphisms or haplotypes was associated with fracture risk or BMD T score <–2.5. BMD and bone turnover were not associated with any of the genetic variants. In conclusion, all the polymorphisms within the IL-1α gene are in strong linkage disequilibrium and not convincingly associated with fracture risk, BMD, or bone turnover.