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

建立基因分析方法以预防类固醇引起的股骨头坏死的发生。

基本信息

批准号：
13470314
负责人：
KUBO Toshikazu
金额：
$ 10.3万
依托单位：
Kyoto prefectural university of medicine.
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470314/
关键词：
Osteonecrosis Steroid Cytochrome P450 Renal transplantation Single nucleotide polymorphism DNA chip DNA Chip

项目摘要

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.

在先进的器官移植技术中，激素性股骨头坏死（ONF）是一种棘手的并发症。激素敏感性在个体间存在差异，提示与激素代谢相关的多种基因多态性参与。本研究探讨细胞色素P450基因单核苷酸多态性（SNP）与ONF发生的关系。受试者为肾移植患者。从外周血中获得基因组DNA，并通过使用各种方法（直接测序、PCR-限制性片段长度多态性和DNA芯片）对CYP 3A 4、CYP 2D 6和CYP 2C 19进行SNP分析。统计分析ONF发生与SNP的关系。CYP 2D 6 ^*2纯合子（优势比：4.7）和CYP 2D 6 ^* 10 B纯合子（优势比：1.8）患者的调整优势比更高，但未观察到显著差异。如果能根据SNPs判断ONF的发生风险，对预防激素性ONF的发生是非常有用的。这一次，与ONF产生明显相关的SNP不被接受，但可能与类固醇代谢相关的SNP的参考是重要的。我们认为有必要从现在开始研究。