Role of platelet-activating factor acetylhydrolase gene mutation in Japanese childhood IgA nephropathy.
Platelet-activating factor (PAF) is a potent mediator of inflammatory injury in renal diseases. PAF is degraded to inactive products by PAF acetylhydrolase. Recently, a point mutation (G to T transversion) of the PAF acetylhydrolase gene was observed at position 994, and this mutation was found to contribute to the variability in plasma PAF levels, with undetectable plasma PAF acetylhydrolase activity occurring in homozygous patients (TT genotype) and reduced levels of activity in heterozygous patients (GT genotype). Therefore, we investigated the effect of the PAF acetylhydrolase gene mutation on the pathogenesis and progression of immunoglobulin A (IgA) nephropathy. Genomic DNA was obtained from 89 children with IgA nephropathy and 100 controls. We identified the PAF acetylhydrolase gene mutation (G994T) by polymerase chain reaction. There was no significant difference in genotypic frequency between patients and controls. However, urinary protein excretion at the time of biopsy was significantly greater in patients with the GT/TT genotypes than in those with the GG genotype. The percentage of glomeruli with mesangial cell proliferation was significantly greater in patients with the GT/TT genotypes than in those with the GG genotype. These results indicate the PAF acetylhydrolase gene mutation may influence the degree of proteinuria and the extent of mesangial proliferation in the early stage of childhood IgA nephropathy.
Tanaka
R
R
Department of Pediatrics, Hyogo Prefectural Awaji Hospital, Sumoto, Hyogo, Japan.
Iijima
K
K
Xu
H
H
Inoue
Y
Y
Murakami
R
R
Shirakawa
T
T
Nishiyama
K
K
Miwa
M
M
Shiozawa
S
S
Nakamura
H
H
Yoshikawa
N
N
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000483:Alleles; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010741:Phospholipases A / Q000097:blood / Q000235:genetics*; D010972:Platelet Activating Factor / Q000032:analysis; D017354:Point Mutation
D010972:Platelet Activating Factor; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D007703:Peptidyl-Dipeptidase A