Genetic association of a polymorphism of the cAMP-responsive element binding protein-binding protein with steroid-induced osteonecrosis after kidney transplantation.
Nontraumatic osteonecrosis (ON) of the femoral head is known to be one of the major complications after organ transplantations. Although the precise mechanism is still uncertain, the administration of glucocorticoid (GC) has been considered to play an important role in the occurrence of ON. To elucidate the genetic factors involved in this pathogenesis, we analyzed single nucleotide polymorphisms (SNP) in the genes for the GC receptor (GR), CYP3A4, cAMP-responsive element binding protein-binding protein (CBP), and nuclear receptor co-activator 2 (NCoA2). Among the patients examined, A/G alleles of the CBP gene were demonstrated in 32.4% of those with ON, but in only 14.6% of those without ON (P = 0.018). No relationships were observed between the SNPs of GR, CYP3A4, and NCoA2 genes and the occurrence of ON. These results indicate that the genetic polymorphism of the CBP, which is one of the essential factors exerting the biological effects of GC, may affect susceptibility to steroid-induced ON in patients after renal transplantation.
Tamura
Kyoko
K
Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2-D5 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nakajima
Shigeo
S
Hirota
Yoshio
Y
Takahashi
Kenji A
KA
Fujioka
Mikihiro
M
Kubo
Toshikazu
T
Iwatani
Yoshinori
Y
Ozono
Keiichi
K
D000293:Adolescent; D000328:Adult; D050882:CREB-Binding Protein / Q000235:genetics*; D016009:Chi-Square Distribution; D002648:Child; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics; D016017:Odds Ratio; D010020:Osteonecrosis / Q000139:chemically induced / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013256:Steroids / Q000009:adverse effects* / Q000627:therapeutic use
D005938:Glucocorticoids; D051958:Nuclear Receptor Coactivator 2; D013256:Steroids; D050882:CREB-Binding Protein
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