title: Low molecular weight phenotype of Apo(a) is a risk factor of corticosteroid-induced osteonecrosis of the femoral head after renal transplant.
abstract: OBJECTIVE
  Osteonecrosis of the femoral head (ONF) is a necrosis due to disruption of the blood flow. The disease often occurs in association with corticosteroid treatment. The pathology of corticosteroid-induced ONF is unclear, although abnormalities in the coagulation and fibrinolytic systems or in the lipid metabolism have been reported to be involved. We examined the relationships between development of ONF and genetic variations and plasma level of lipoprotein(a) (Lp(a)), which is closely involved in the coagulation and fibrinolytic systems and lipid metabolism.
  
  
  METHODS
  The study population consisted of 112 renal transplant patients undergoing corticosteroid treatment. Their apolipoprotein (a) [apo(a)] isoform was determined by Western blotting, and patients were classified into low molecular weight (LMW) or high molecular weight (HMW) groups. The plasma Lp(a) level was measured. Patients were also examined for 3 single-nucleotide polymorphisms (SNP), -773 (G/A), +93 (C/T), and +121 (G/A). Relationships between these 3 genetic factors of Lp(a) and ONF development were examined using statistical methods including multivariate analysis.
  
  
  RESULTS
  A strong relationship was observed between the apo(a) molecular weight phenotype and ONF development, with an increased risk of ONF development for the LMW group (adjusted odds ratio 5.75, 95% CI 1.76-18.74, p = 0.0038). No significant relationships were observed between ONF and plasma Lp(a) level and SNP.
  
  
  CONCLUSIONS
  Apo(a) molecular weight phenotype would be a useful predictor of ONF that develops after corticosteroid treatment.
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Hirata
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Fujioka
authors.forename: Kenji A
authors.initials: KA
authors.lastname: Takahashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Asano
authors.forename: Masashi
authors.initials: M
authors.lastname: Ishida
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Akioka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Okamoto
authors.forename: Norio
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Satomi
authors.forename: Hoyoku
authors.initials: H
authors.lastname: Nishino
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirota
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakajima
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kubo
mesh_terms: D053241:Apoprotein(a) / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D015415:Biomarkers; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D005342:Fibrinolysis / Q000502:physiology; D005938:Glucocorticoids / Q000009:adverse effects*; D006239:Haplotypes / Q000502:physiology; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011239:Prednisolone / Q000009:adverse effects*; D012307:Risk Factors; D019851:Thrombophilia / Q000097:blood / Q000235:genetics / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D011239:Prednisolone; D053241:Apoprotein(a)