Establishment of gene analytic method to prevent the development of the steroid induced osteonecrosis of the femoral head.

在先进的器官移植技术中，激素性股骨头坏死(ONF)是最棘手的并发症之一。不同个体对类固醇的敏感性不同，提示与类固醇代谢相关的多个基因的多态有关。本研究探讨细胞色素P450 DNA序列的单核苷酸多态(SNP)与ONF发生的关系。受试者为肾移植患者。从患者外周血中提取基因组DNA，采用直接测序、聚合酶链式反应-限制性片段长度多态性和DNA芯片等方法对其进行单核苷酸多态分析。对ONF的发展与SNP的关系进行了统计分析。具有CYP2D6^*2纯合子(优势比：4.7)和CYP2D6^*10B纯合子(优势比：1.8)的患者调整后优势比较高，但差异无统计学意义。如果根据SNPs判断发生风险对预防激素性ONF是非常有用的。这一次，它与ONF产生明显相关的SNPs没有被接受，但可能与类固醇代谢相关的SNPs的参考是重要的。我们认为，从现在开始有必要进行审查。

In advanced organ transplantation technology, steroid-induced osteonecrosis of femoral head (ONF) is one of troublesome complications. Steroid sensitivity could vary in individuals, and the involvement of polymorphism of various gene which relates to the steroid metabolism is suggested. The present study investigated the relationship between single nucleotide polymorphism (SNP) on DNA sequence of cytochrome P450 and ONF development. Subjects were renal transplant patients. Genome DNA was obtained from the peripheral blood, and SNP analyses for CYP3A4, CYP2D6 and CYP2C19 were conducted by using various methods ; direct sequencing, PCR-restriction fragment length polymorphism and DNA Chip. Statistical analysis on the relationship between ONF development and SNP was done. Adusted odds ratio was higher in patients who had CYP2D6^*2 homozygote (odds ratio : 4.7) and CYP2D6^*10B homozygote (odds ratio : 1.8), while significant difference was not observed. It is very useful if the generating risk judging according to SNPs to prevention of steroid induced ONF is possible. This time, SNPs to which it is clearly related with ONF generating was not accepted, but reference of SNPs which may be related to steroid metabolism is important. We think that it is necessary to examine from now on.