Asano Takeshi, Takahashi Kenji A, Fujioka Mikihiro, Inoue Shigehiro, Ueshima Keiichiro, Hirata Tetsurou, Okamoto Masahiko, Satomi Yoshiko, Nishino Hoyoku, Tanaka Takashi, Hirota Yoshio, Kubo Toshikazu
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Transplantation. 2004 Jan 27;77(2):220-5. doi: 10.1097/01.TP.0000101433.99651.96.
Nontraumatic osteonecrosis of the femoral head (ONFH) is one of the complications that may occur after renal transplantation. We investigated the relationship between the incidence of ONFH and polymorphisms in the genes for plasminogen activator inhibitor (PAI)-1, which is one of the major regulatory proteins of the fibrinolytic system, and 5,10-methylenetetrahydrofolate reductase (MTHFR), which is associated with the plasma levels of homocysteine in Japanese subjects.
Thirty-one patients with postrenal transplant ONFH and 106 patients without ONFH were selected. Genotypes of PAI-1 4G/5G and MTHFR C677T were determined by direct sequencing of genomic DNA. In addition, plasma PAI-1 antigen (Ag) levels and plasma total homocysteine (tHcy) levels at the steady state were measured. The relationships between the incidence of ONFH and these genotypes, as well as plasma levels of the gene products, were investigated.
Plasma PAI-1 Ag levels were the highest in patients with the 4G/4G genotype, and plasma tHcy levels were the highest in patients with TT genotypes of MTHFR C677T. However, the relationship between the incidence of ONFHH and PAI-1 4G/5G or MTHFR C677T was not observed. The relationship between the incidence of ONFH and plasma levels of PAI-1 Ag or tHcy was not observed.
Genotypes of PAI-1 4G/5G and MTHFR C677T or plasma concentrations of PAI-1 Ag and tHcy had no effect on the incidence of ONFH in Japanese subjects, unlike the results of studies performed in white subjects. The effect of genetic background on the pathologic conditions that developed in patients with postrenal transplant ONFH may differ according to race.
非创伤性股骨头坏死（ONFH）是肾移植后可能发生的并发症之一。我们研究了纤溶酶原激活物抑制剂（PAI）-1基因多态性与ONFH发病率之间的关系，PAI-1是纤维蛋白溶解系统的主要调节蛋白之一；还研究了5,10-亚甲基四氢叶酸还原酶（MTHFR）基因多态性与ONFH发病率之间的关系，MTHFR与日本受试者血浆同型半胱氨酸水平相关。
选取31例肾移植后发生ONFH的患者和106例未发生ONFH的患者。通过对基因组DNA进行直接测序来确定PAI-1 4G/5G和MTHFR C677T的基因型。此外，还测量了稳态时血浆PAI-1抗原（Ag）水平和血浆总同型半胱氨酸（tHcy）水平。研究了ONFH发病率与这些基因型以及基因产物血浆水平之间的关系。
4G/4G基因型患者的血浆PAI-1 Ag水平最高，MTHFR C677T的TT基因型患者的血浆tHcy水平最高。然而，未观察到ONFH发病率与PAI-1 4G/5G或MTHFR C67/T之间的关系。也未观察到ONFH发病率与血浆PAI-1 Ag或tHcy水平之间的关系。
与在白人受试者中进行的研究结果不同，PAI-1 4G/5G和MTHFR C677T的基因型或PAI-1 Ag和tHcy的血浆浓度对日本受试者ONFH的发病率没有影响。肾移植后发生ONFH的患者所出现的病理状况受遗传背景的影响可能因种族而异。
