Low molecular weight phenotype of Apo(a) is a risk factor of corticosteroid-induced osteonecrosis of the femoral head after renal transplant.
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.
Hirata
Tetsurou
T
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Fujioka
Mikihiro
M
Takahashi
Kenji A
KA
Asano
Takeshi
T
Ishida
Masashi
M
Akioka
Kiyokazu
K
Okamoto
Masahiko
M
Yoshimura
Norio
N
Satomi
Yoshiko
Y
Nishino
Hoyoku
H
Hirota
Yoshio
Y
Nakajima
Shigeo
S
Kato
Shigeaki
S
Kubo
Toshikazu
T
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
D015415:Biomarkers; D005938:Glucocorticoids; D011239:Prednisolone; D053241:Apoprotein(a)