Bustamante Mariona, Nogués Xavier, Agueda Lídia, Jurado Susana, Wesselius Anke, Cáceres Enrique, Carreras Ramon, Ciria Manel, Mellibovsky Leonardo, Balcells Susana, Díez-Pérez Adolfo, Grinberg Daniel
Department of Genetics, University of Barcelona, Av Diagonal, 645, E-08028, Barcelona, Spain.
Calcif Tissue Int. 2007 Oct;81(4):327-32. doi: 10.1007/s00223-007-9069-2. Epub 2007 Sep 19.
Stimulation of bone formation is a key therapeutic target in osteoporosis. Runx2 is a runt domain transcription factor essential to osteoblast differentiation, bone remodeling, and fracture healing. Runx2 knockout mice exhibit a complete lack of ossification, while overexpression of this gene in transgenic mice results in an osteoporotic phenotype. Thus, RUNX2 is a good candidate for the genetic determination of osteoporosis. In this association study, the effects of the -330 G/T polymorphism in promoter 1 and the -1025 T/C polymorphism (rs7771980) in promoter 2 of RUNX2 were tested in relation to lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) in a cohort of 821 Spanish postmenopausal women. The minor allele frequencies for the two polymorphisms were 0.15 and 0.07, respectively. The two polymorphisms, located more than 90 kb apart, were not in linkage disequilibrium (D' = 0.27, r (2) = 0.028). In an ANCOVA test adjusting by weight, height, age, and years since menopause, the -330 G/T polymorphism was not associated with any of the phenotypes analyzed, while we found the -1025 T/C polymorphism to be associated with FN BMD (p = 0.001). In particular, individuals carrying the TC genotype had higher mean adjusted FN BMD values than those bearing the TT genotype. Our results highlight the importance of this RUNX2 promoter 2 polymorphism in FN BMD determination.
刺激骨形成是骨质疏松症的关键治疗靶点。Runx2是一种 runt 结构域转录因子，对成骨细胞分化、骨重塑和骨折愈合至关重要。Runx2基因敲除小鼠表现出完全缺乏骨化，而该基因在转基因小鼠中的过表达则导致骨质疏松表型。因此，RUNX2是骨质疏松症遗传决定因素的一个良好候选基因。在这项关联研究中，对821名西班牙绝经后女性队列中RUNX2启动子1的 -330 G/T多态性和启动子2的 -1025 T/C多态性（rs7771980）与腰椎（LS）和股骨颈（FN）骨密度（BMD）的关系进行了测试。这两种多态性的次要等位基因频率分别为0.15和0.07。这两种相距超过90 kb的多态性不存在连锁不平衡（D' = 0.27，r(2) = 0.028）。在一项通过体重、身高、年龄和绝经后年限进行校正的协方差分析测试中，-330 G/T多态性与所分析的任何表型均无关联，而我们发现 -1025 T/C多态性与股骨颈骨密度相关（p = 0.001）。特别是，携带TC基因型的个体经调整后的股骨颈骨密度平均值高于携带TT基因型的个体。我们的结果突出了RUNX2启动子2多态性在股骨颈骨密度测定中的重要性。
