title: Genetic association of a polymorphism of the cAMP-responsive element binding protein-binding protein with steroid-induced osteonecrosis after kidney transplantation.
abstract: 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.
authors: Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2-D5 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Kyoko
authors: K
authors: Tamura
authors: Shigeo
authors: S
authors: Nakajima
authors: Yoshio
authors: Y
authors: Hirota
authors: Kenji A
authors: KA
authors: Takahashi
authors: Mikihiro
authors: M
authors: Fujioka
authors: Toshikazu
authors: T
authors: Kubo
authors: Yoshinori
authors: Y
authors: Iwatani
authors: Keiichi
authors: K
authors: Ozono
mesh_terms: 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
chemical_list: D005938:Glucocorticoids; D051958:Nuclear Receptor Coactivator 2; D013256:Steroids; D050882:CREB-Binding Protein
references: Drug Metab Pharmacokinet. 2005 Feb;20(1):79-84
references: 15770078
references: J Clin Endocrinol Metab. 1998 May;83(5):1814-7
references: 9589699
references: Nucleic Acids Res. 2002 Jan 1;30(1):158-62
references: 11752280
references: Transplant Proc. 1998 Nov;30(7):3039-40
references: 9838339
references: Nature. 1994 Jan 20;367(6460):284-7
references: 8161378
references: Nature. 1993 Oct 28;365(6449):855-9
references: 8413673
references: J Bone Miner Metab. 2003;21(4):225-8
references: 12811627
references: Nature. 1997 Sep 25;389(6649):349-52
references: 9311776
references: J Clin Endocrinol Metab. 1998 Jan;83(1):144-51
references: 9435432
references: J Biol Chem. 2001 Apr 27;276(17 ):13505-8
references: 11279224
references: Am J Obstet Gynecol. 1999 May;180(5):1115-20
references: 10329864
references: Cell. 1996 May 3;85(3):403-14
references: 8616895
references: Mol Endocrinol. 2006 May;20(5):1138-52
references: 16423883
references: Nat Genet. 2005 Feb;37(2):138-44
references: 15640800
references: Nat Med. 2001 Mar;7(3):285-7
references: 11231620
references: J Pharmacol Exp Ther. 1994 Jul;270(1):414-23
references: 8035341
references: Obes Res. 1997 May;5(3):186-92
references: 9192392
references: Mol Cell Endocrinol. 2000 Jan 25;159(1-2):45-51
references: 10687851
references: Microbiol Mol Biol Rev. 2000 Jun;64(2):435-59
references: 10839822
references: Br J Hosp Med. 1994 Mar 16-Apr 5;51(6):275-80
references: 8032562
references: Lancet. 1995 May 13;345(8959):1238-9
references: 7605460
references: Endocr Rev. 2005 Jun;26(4):583-97
references: 15561801
references: Calcif Tissue Int. 1999 Nov;65(5):352-3
references: 10541758
references: J Biol Chem. 1999 Jan 22;274(4):1879-82
references: 9890939
references: J Mol Endocrinol. 1992 Dec;9(3):295-300
references: 1362060
references: J Bone Miner Res. 1996 Mar;11(3):306-11
references: 8852941
references: Mol Cell Biol. 2002 Apr;22(7):1961-70
references: 11884585
references: Am J Clin Dermatol. 2001;2(6):377-88
references: 11770392
references: J Orthop Sci. 2003;8(3):329-33
references: 12768474
references: Pharmacol Toxicol. 1993 Feb;72(2):78-83
references: 8474968
references: J Steroid Biochem Mol Biol. 1997 Jul;62(4):345-52
references: 9408089
references: N Engl J Med. 2003 Feb 6;348(6):538-49
references: 12571262
references: Pharmacogenetics. 2003 Nov;13(11):675-82
references: 14583680
references: Endocr Rev. 2003 Aug;24(4):488-522
references: 12920152
references: Hypertension. 1996 Sep;28(3):478-82
references: 8794836