Genetic analysis of steroid-induced osteonecrosis of the femoral head.
With advanced organ transplantation technology, steroid-induced osteonecrosis of the femoral head (ONF) is one of the most troublesome complications. Steroid sensitivity varies among individuals, and the involvement of polymorphism of various genes relating to steroid metabolism is suggested. The present study investigated the relation between single nucleotide polymorphism (SNP) on the DNA sequence of cytochrome p(450) and ONF development. The subjects were 80 renal transplant patients. Genome DNA was obtained from the peripheral blood, and SNP analyses for CYP3A4, CYP2D6, and CYP2C19 were conducted using various methods: direct sequencing, polymerase chain reaction restriction fragment length polymorphism, and DNA Chip. The relation between ONF development and SNP was statistically analyzed. It is useful if the generating risk judged according to SNPs to prevention of steroid-induced ONF is possible. This time, SNPs, which are clearly related to ONF, were not accepted, although the possibility that SNP related to steroid metabolism is involved in ONF development is important. We think that it is necessary to examine this area more closely.
Asano
Takeshi
T
Department of Orthopaedic Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Takahashi
Kenji A
KA
Fujioka
Mikihiro
M
Inoue
Shigehiro
S
Satomi
Yoshiko
Y
Nishino
Hoyoku
H
Tanaka
Takashi
T
Hirota
Yoshio
Y
Takaoka
Kunio
K
Nakajima
Shigeo
S
Kubo
Toshikazu
T
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000235:genetics; D005938:Glucocorticoids / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D016030:Kidney Transplantation; D006899:Mixed Function Oxygenases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C104464:CYP3A protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human