Glueck Charles J, Freiberg Richard A, Oghene Jennifer, Fontaine Robert N, Wang Ping
Cholesterol Center, Jewish Hospital of Cincinnati, 3200 Burnet Avenue, Cincinnati, OH 45229, USA.
J Bone Joint Surg Am. 2007 Nov;89(11):2460-8. doi: 10.2106/JBJS.F.01421.
Nitric oxide regulates bone turnover by osteoblasts and osteoclasts. Nitric oxide production is impaired by the T-786C eNOS single nucleotide polymorphism, with a substitution of the nucleotide thymine by cytosine at a locus 786 base pairs upstream of the eNOS gene. This leads to vasoconstriction, platelet aggregation, reduced angiogenesis, and reduced bone formation, all of which may be associated with osteonecrosis of the hip. We studied relationships between the T-786C eNOS polymorphism and idiopathic and secondary necrosis of the head of the femur in order to better understand the pathophysiology of osteonecrosis.
With use of polymerase chain reaction methodology, the T-786C eNOS polymorphism was compared in ninety-five patients with femoral head necrosis (including thirty-six nonsmokers with idiopathic necrosis and fifty-nine patients with secondary necrosis) and seventy-two healthy normal adult controls.
Homozygosity for the mutant eNOS allele (TT) was present in eight (22%) of thirty-six patients with idiopathic osteonecrosis as compared with one (3%) of thirty-six race, gender, and age-matched controls; heterozygosity (TC) was present in nineteen patients (53%) as compared with ten controls (28%); and the wild-type normal genotype (CC) was present in nine patients (25%) as compared with twenty-five controls (69%) (p = 0.0004). Logistic regression revealed that the T-786C eNOS mutant allele was positively associated with idiopathic osteonecrosis of the femoral head (odds ratio, 6.0; 95% confidence interval, 2.51 to 14.4). The fifty-nine patients with secondary osteonecrosis did not differ from fifty-two race, gender, and age-matched controls in terms of the distribution of the T-786C eNOS polymorphism (p = 0.19) or in terms of mutant allele frequency (30% compared with 21%; p = 0.15). The thirty-six patients with idiopathic osteonecrosis differed from the fifty-nine patients with secondary osteonecrosis in that they were more likely to have mutant eNOS genotypes (p = 0.033) and to have a higher mutant T allele frequency (49% compared with 30%; p = 0.009).
The T-786C eNOS polymorphism and resultant reduction of nitric oxide production is associated with, and may contribute to, the pathogenesis of idiopathic osteonecrosis of the femoral head.
Prognostic Level III. See Instructions to Authors for a complete description of levels of evidence.
一氧化氮通过成骨细胞和破骨细胞调节骨转换。T-786C内皮型一氧化氮合酶（eNOS）单核苷酸多态性会损害一氧化氮的生成，在eNOS基因上游786个碱基对处的一个位点，胸腺嘧啶核苷酸被胞嘧啶取代。这会导致血管收缩、血小板聚集、血管生成减少以及骨形成减少，所有这些都可能与股骨头坏死有关。我们研究了T-786C eNOS多态性与特发性和继发性股骨头坏死之间的关系，以便更好地理解骨坏死的病理生理学。
采用聚合酶链反应方法，对95例股骨头坏死患者（包括36例非吸烟的特发性坏死患者和59例继发性坏死患者）和72例健康正常成年对照者的T-786C eNOS多态性进行比较。
36例特发性骨坏死患者中有8例（22%）为突变型eNOS等位基因纯合子（TT），而在36例种族、性别和年龄匹配的对照者中有1例（3%）；杂合子（TC）在19例患者中出现（53%），而对照者中有10例（28%）；野生型正常基因型（CC）在9例患者中出现（25%），而对照者中有25例（69%）（p = 0.0004）。逻辑回归显示，T-786C eNOS突变等位基因与股骨头特发性骨坏死呈正相关（比值比，6.0；95%置信区间，2.51至14.4）。59例继发性骨坏死患者在T-786C eNOS多态性分布方面（p = 0.19）或突变等位基因频率方面（30% 与21%相比；p = 0.15）与52例种族、性别和年龄匹配的对照者没有差异。36例特发性骨坏死患者与59例继发性骨坏死患者的不同之处在于，他们更有可能具有突变型eNOS基因型（p = 0.033）且突变T等位基因频率更高（49% 与30%相比；p = 0.009）。
T-786C eNOS多态性以及由此导致的一氧化氮生成减少与股骨头特发性骨坏死的发病机制相关，并且可能起一定作用。
预后水平III。有关证据水平的完整描述见作者须知。
