Department of Orthopaedics, Chaoyang Hospital, Capital Medical University, Beijing, China.
Chin Med J (Engl). 2010 Sep;123(18):2537-42.
Several candidate genes of ossification of the posterior longitudinal ligament (OPLL) susceptibility have been identified, but their polymorphisms account for only a small percent of the total variance. Bone morphogenetic protein-4 (BMP4) is a potent ectopic ossification inducing factor. BMP4 protein and mRNA are present in cells from OPLL patients, but not non-OPLL controls. A single nucleotide polymorphism of 6007C>T(rs17563) of BMP4 has been reported to affect bone density in postmenopausal women. Thus, BMP4 may function in OPLL development. Appropriately, the relationship between BMP4 polymorphisms and OPLL was investigated.
A case-control association study investigated the genetic etiology in 179 OPLL patients and 298 non-OPLL controls. Extent of OPLL was analyzed by radiologic examinations. Whether single nucleotide polymorphism (SNP) of -5826G>A(rs1957860) 5' of the transcription start site and 6007C>T(rs17563) in exon 4 of the BMP4 gene were statistically associated with genetic susceptibility to OPLL in Chinese Han subjects was assessed.
A significant statistical difference in genotype of 6007C>T polymorphism between male OPLL patients and male controls was evident, and the frequency of "TT" genotype in male OPLL patients was significantly higher than in male controls (P = 0.039). The frequency of the "T" allele was also significantly higher in male OPLL subjects than in male controls (P = 0.014, OR = 1.57). A significant difference was also observed between the 6007C>T polymorphism and the number of ossified cervical vertebrae in OPLL patients, while no statistical difference was apparent between the -5826G>A polymorphism and OPLL occurrence.
The T allele in the 6007C>T polymorphism may be a risk factor for male Han Chinese with ossification of the posterior longitudinal ligament in the cervical spine. Chinese Han male patients with CT and TT 6007C>T genotypes have a genetic susceptibility to OPLL and more extensive OPLL in the cervical spine.
已经发现了几个与后纵韧带骨化（OPLL）易感性相关的候选基因，但它们的多态性仅占总方差的一小部分。骨形态发生蛋白 4（BMP4）是一种有效的异位骨化诱导因子。OPLL 患者的细胞中存在 BMP4 蛋白和 mRNA，但非 OPLL 对照中不存在。据报道，BMP4 基因的 6007C>T(rs17563)单核苷酸多态性会影响绝经后妇女的骨密度。因此，BMP4 可能在 OPLL 发病机制中起作用。因此，研究了 BMP4 多态性与 OPLL 之间的关系。
对 179 例 OPLL 患者和 298 例非 OPLL 对照进行病例对照关联研究，分析 OPLL 的严重程度。通过放射学检查评估单核苷酸多态性（SNP）-5'转录起始位点的-5826G>A(rs1957860)和 BMP4 基因外显子 4 中的 6007C>T(rs17563)是否与中国汉族人群 OPLL 的遗传易感性相关。
男性 OPLL 患者与男性对照组之间 6007C>T 多态性的基因型存在显著统计学差异，男性 OPLL 患者“TT”基因型的频率明显高于男性对照组（P=0.039）。男性 OPLL 患者的“T”等位基因频率也明显高于男性对照组（P=0.014，OR=1.57）。6007C>T 多态性与 OPLL 患者的骨化颈椎数之间也存在显著差异，而-5826G>A 多态性与 OPLL 发生之间无明显差异。
6007C>T 多态性中的 T 等位基因可能是汉族男性颈椎后纵韧带骨化的危险因素。汉族男性 CT 和 TT 6007C>T 基因型的患者对 OPLL 有遗传易感性，颈椎 OPLL 更为广泛。
