ApoB C7623T polymorphism predicts risk for steroid-induced osteonecrosis of the femoral head after renal transplantation.
BACKGROUND
Nontraumatic osteonecrosis of the femoral head (ONFH) is caused by disruption of blood flow. This disease often occurs in association with steroid treatment. The pathology of steroid-induced ONFH remains unclear, although abnormalities in lipid metabolism have been reported to be involved. In this study, we examined the differences of gene polymorphism frequencies of apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), which are important proteins for lipid transport, as well as of lipid parameters, between ONFH cases and referent patients among those who were subjected to renal transplantation.


METHODS
Subjects were 158 cases who had undergone renal transplant, including 34 cases that were diagnosed as ONFH after renal transplantation and 124 cases that were not. Four single nucleotide polymorphisms including C7623T and G12619A for the ApoB gene and G75A and C83T for the ApoA1 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman real-time PCR chemistry. Also, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), ApoB, and ApoA1 were measured. Their relationship to ONFH was statistically evaluated.


RESULTS
A higher frequency of 7623TT or CT of the ApoB gene was observed in ONFH cases than in referent patients (P = 0.033), resulting in an elevated odds ratio that was statistically significant (adjusted odds ratio = 6.37, 95% CI = 1.53-26.5, P = 0.011). No significant relationship was observed between other genes and ONFH. Regarding lipid parameters, a higher value of ApoB/ApoA1 ratio was observed in cases (P = 0.045).


CONCLUSIONS
For the prediction of ONFH, it is useful to analyze ApoB C7623T and plasma ApoB/ApoA1 ratio before the administration of steroids.
Hirata
Tetsurou
T
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-chou, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
Fujioka
Mikihiro
M
Takahashi
Kenji A
KA
Arai
Yuji
Y
Asano
Takeshi
T
Ishida
Masashi
M
Kuribayashi
Masaaki
M
Akioka
Kiyokazu
K
Okamoto
Masahiko
M
Yoshimura
Norio
N
Satomi
Yoshiko
Y
Nishino
Hoyoku
H
Fukushima
Wakaba
W
Hirota
Yoshio
Y
Nakajima
Shigeo
S
Kato
Shigeaki
S
Kubo
Toshikazu
T
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002648:Child; D004247:DNA / Q000235:genetics*; D005260:Female; D005271:Femur Head Necrosis / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D005500:Follow-Up Studies; D005787:Gene Frequency; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007275:Injections, Intravenous; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011183:Postoperative Complications; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D015415:Biomarkers; D005938:Glucocorticoids; D004247:DNA; D011239:Prednisolone