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Low Molecular Weight Phenotype of Apolipoprotein(a) Is a Risk Factor of Corticosteroid-Induced Osteonecrosis of the Femoral Head After Renal Transplant
TETSUROU HIRATA, MIKIHIRO FUJIOKA, KENJI A. TAKAHASHI, TAKESHI ASANO, MASASHI ISHIDA, KIYOKAZU AKIOKA, MASAHIKO OKAMOTO, NORIO YOSHIMURA, YOSHIKO SATOMI, HOYOKU NISHINO, YOSHIO HIROTA, SHIGEO NAKAJIMA, SHIGEAKI KATO, and TOSHIKAZU KUBO 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. Conclusion. Apo(a) molecular weight phenotype would be a useful predictor of ONF that develops after corticosteroid treatment. (First Release Dec 1 2006; J Rheumatol 2007;34:516-22) Key Indexing Terms:
CORTICOSTEROIDS From the Department of Orthopaedics; Department of Transplantation and Regenerative Surgery; Department of Organ Interaction Research Medicine; and Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto; Department of Public Health, Faculty of Medicine, Osaka City University, Osaka; Department of Developmental Medicine (Pediatrics), Osaka University Graduate School of Medicine, Osaka; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan. Supported by the Japanese Investigation Committee for Osteonecrosis of the Femoral Head, under the auspices of the Ministry of Health and Welfare of Japan. T. Hirata, MD, Graduate Student; M. Fujioka, MD, PhD, Assistant Professor; K.A. Takahashi, MD, PhD, Assistant Professor; T. Asano, MD, PhD; M. Ishida, MD, Department of Orthopaedics; K. Akioka, MD, PhD, Assistant Professor, Department of Transplantation and Regenerative Surgery; M. Okamoto, MD, PhD, Associate Professor, Department of Organ Interaction Research Medicine; N. Yoshimura, MD, PhD, Professor, Department of Transplantation and Regenerative Surgery; Y. Satomi, PhD, Assistant Professor; H. Nishino, MD, PhD, Professor, Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine; Y. Hirota, MD, PhD, Professor, Department of Public Health, Faculty of Medicine, Osaka City University; S. Nakajima, MD, PhD, Associate Professor, Department of Developmental Medicine (Pediatrics), Osaka University Graduate School of Medicine; S. Kato, MD, PhD, Professor, Institute of Molecular and Cellular Biosciences, University of Tokyo; T. Kubo, MD, PhD, Professor, Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine. Address reprint requests to Prof. T. Kubo, Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-chou, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan. E-mail: tkubo@koto.kpu-m.ac.jp Accepted for publication September 8, 2006.
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