Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects.
BACKGROUND
Nontraumatic osteonecrosis of the femoral head (ONFH) is one of the complications that may occur after renal transplantation. We investigated the relationship between the incidence of ONFH and polymorphisms in the genes for plasminogen activator inhibitor (PAI)-1, which is one of the major regulatory proteins of the fibrinolytic system, and 5,10-methylenetetrahydrofolate reductase (MTHFR), which is associated with the plasma levels of homocysteine in Japanese subjects.


METHODS
Thirty-one patients with postrenal transplant ONFH and 106 patients without ONFH were selected. Genotypes of PAI-1 4G/5G and MTHFR C677T were determined by direct sequencing of genomic DNA. In addition, plasma PAI-1 antigen (Ag) levels and plasma total homocysteine (tHcy) levels at the steady state were measured. The relationships between the incidence of ONFH and these genotypes, as well as plasma levels of the gene products, were investigated.


RESULTS
Plasma PAI-1 Ag levels were the highest in patients with the 4G/4G genotype, and plasma tHcy levels were the highest in patients with TT genotypes of MTHFR C677T. However, the relationship between the incidence of ONFHH and PAI-1 4G/5G or MTHFR C677T was not observed. The relationship between the incidence of ONFH and plasma levels of PAI-1 Ag or tHcy was not observed.


CONCLUSIONS
Genotypes of PAI-1 4G/5G and MTHFR C677T or plasma concentrations of PAI-1 Ag and tHcy had no effect on the incidence of ONFH in Japanese subjects, unlike the results of studies performed in white subjects. The effect of genetic background on the pathologic conditions that developed in patients with postrenal transplant ONFH may differ according to race.
Asano
Takeshi
T
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Takahashi
Kenji A
KA
Fujioka
Mikihiro
M
Inoue
Shigehiro
S
Ueshima
Keiichiro
K
Hirata
Tetsurou
T
Okamoto
Masahiko
M
Satomi
Yoshiko
Y
Nishino
Hoyoku
H
Tanaka
Takashi
T
Hirota
Yoshio
Y
Kubo
Toshikazu
T
D000293:Adolescent; D000328:Adult; D044466:Asian People; D002648:Child; D005260:Female; D005269:Femur / Q000473:pathology*; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010020:Osteonecrosis / Q000453:epidemiology / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1; D042965:Methylenetetrahydrofolate Reductase (NADPH2)