Hirata Tetsurou, Fujioka Mikihiro, Takahashi Kenji A, Arai Yuji, Asano Takeshi, Ishida Masashi, Kuribayashi Masaaki, Akioka Kiyokazu, Okamoto Masahiko, Yoshimura Norio, Satomi Yoshiko, Nishino Hoyoku, Fukushima Wakaba, Hirota Yoshio, Nakajima Shigeo, Kato Shigeaki, Kubo Toshikazu
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-chou, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
J Orthop Sci. 2007 May;12(3):199-206. doi: 10.1007/s00776-007-1110-9. Epub 2007 May 31.
Nontraumatic osteonecrosis of the femoral head (ONFH) is caused by disruption of blood flow. This disease often occurs in association with steroid treatment. The pathology of steroid-induced ONFH remains unclear, although abnormalities in lipid metabolism have been reported to be involved. In this study, we examined the differences of gene polymorphism frequencies of apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), which are important proteins for lipid transport, as well as of lipid parameters, between ONFH cases and referent patients among those who were subjected to renal transplantation.
Subjects were 158 cases who had undergone renal transplant, including 34 cases that were diagnosed as ONFH after renal transplantation and 124 cases that were not. Four single nucleotide polymorphisms including C7623T and G12619A for the ApoB gene and G75A and C83T for the ApoA1 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman real-time PCR chemistry. Also, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), ApoB, and ApoA1 were measured. Their relationship to ONFH was statistically evaluated.
A higher frequency of 7623TT or CT of the ApoB gene was observed in ONFH cases than in referent patients (P = 0.033), resulting in an elevated odds ratio that was statistically significant (adjusted odds ratio = 6.37, 95% CI = 1.53-26.5, P = 0.011). No significant relationship was observed between other genes and ONFH. Regarding lipid parameters, a higher value of ApoB/ApoA1 ratio was observed in cases (P = 0.045).
For the prediction of ONFH, it is useful to analyze ApoB C7623T and plasma ApoB/ApoA1 ratio before the administration of steroids.
非创伤性股骨头坏死（ONFH）是由血流中断引起的。这种疾病常与类固醇治疗相关。尽管有报道称脂质代谢异常与之有关，但类固醇诱导的ONFH的病理机制仍不清楚。在本研究中，我们检测了肾移植患者中ONFH病例与对照患者之间，载脂蛋白B（ApoB）和载脂蛋白A1（ApoA1）（脂质转运的重要蛋白质）的基因多态性频率差异以及脂质参数差异。
研究对象为158例接受肾移植的患者，其中34例在肾移植后被诊断为ONFH，124例未患ONFH。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和Taqman实时PCR技术分析了ApoB基因的C7623T和G12619A以及ApoA1基因的G75A和C83T这四个单核苷酸多态性。此外，还测量了血清低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、ApoB和ApoA1水平。对它们与ONFH的关系进行了统计学评估。
ONFH病例中ApoB基因7623TT或CT的频率高于对照患者（P = 0.033），导致优势比升高，具有统计学意义（调整后的优势比 = 6.37，95%CI = 1.53 - 26.5，P = 0.011）。未观察到其他基因与ONFH之间存在显著关系。关于脂质参数，病例组的ApoB/ApoA1比值较高（P = 0.045）。
对于ONFH的预测，在使用类固醇之前分析ApoB C7623T和血浆ApoB/ApoA1比值是有用的。
