Combination analysis of three polymorphisms for predicting the risk for steroid-induced osteonecrosis of the femoral head.
BACKGROUND
Osteonecrosis of the femoral head (ONF) often develops following corticosteroid administration. We previously investigated the genetic background for the development of corticosteroid-induced ONF and found relations between ONF development and genetic polymorphisms in the ATP binding cassette B1 (ABCB1) gene (C3435T), apolipoprotein B (ApoB) gene (C7623T), and cAMP-response element binding protein-binding protein (CBP) gene (rs3751845). In the present study, we examined whether combined information regarding these three single nucleotide polymorphisms (SNPs) in the ABCB1, ApoB, and CBP genes is useful for predicting ONF development.


METHODS
A case-control study was performed to study the development of corticosteroid-induced ONF. The cases were 34 patients who developed ONF, and the references were 123 patients who did not develop ONF. To evaluate the presence of interactions among the ABCB1, ApoB, and CBP genes, a synergistic index was calculated using an additive model.


RESULTS
The synergistic index between the ABCB1 and CBP genes was >1.00 (1.99), revealing the presence of an interaction.


CONCLUSIONS
Through analysis of multiple genes that may affect ONF development, we have shown a possible relation among genes encoding completely different proteins. We believe that analysis of the interactions among these genes can contribute to elucidating the mechanism of ONF development in addition to enabling identification of high-risk patients for ONF development.
Kuribayashi
Masaaki
M
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
Fujioka
Mikihiro
M
Takahashi
Kenji A
KA
Arai
Yuji
Y
Hirata
Tetsurou
T
Nakajima
Shigeo
S
Yoshimura
Norio
N
Satomi
Yoshiko
Y
Nishino
Hoyoku
H
Kondo
Kyoko
K
Fukushima
Wakaba
W
Hirota
Yoshio
Y
Kubo
Toshikazu
T
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics; D015415:Biomarkers; D050882:CREB-Binding Protein / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013256:Steroids / Q000009:adverse effects*; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001055:Apolipoproteins B; D015415:Biomarkers; D013256:Steroids; D050882:CREB-Binding Protein; C494363:CREBBP protein, human