Association of the uteroglobin gene polymorphism with IgA nephropathy.
Immunoglobulin A (IgA) nephropathy results from the abnormal deposition of IgA in the renal mesangium. Genetic factors may be involved in the development and progression of IgA nephropathy. Uteroglobin (UG) is a steroid-inducible, cytokine-like, multifunctional protein with anti-inflammatory and immunomodulatory properties. The knockout or antisense mouse of the UG gene develops renal disease similar to IgA nephropathy. We analyzed the UG gene as a candidate for a predisposing factor in 61 Japanese patients with IgA nephropathy (23 children, 38 adults) and detected only the G38A mutation. The gene frequency of the G38A mutation in patients was 0.43, not significantly different from the frequency of 0.36 in healthy controls. However, the frequency of patients homozygous for G38A was twice that of controls, and a significant increase was seen in child patients. We measured serum UG levels in patients and healthy adults. A significant decrease in serum UG levels in homozygotes of G38A compared with homozygotes of G38 was detected only in adult women patients and controls. There is no information on where serum UG is produced or how UG may work in association with IgA nephropathy. However, it is possible that the effect of G38A may be apparent under such stimulation as sex steroids or infections, and homozygotes of the G38A mutation cannot produce sufficient UG in response to stimulation and may be predisposed to IgA nephropathy, especially in childhood.
Matsunaga
Akira
A
Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
Numakura
Chikahiko
C
Kawakami
Takako
T
Itoh
Yoshihisa
Y
Kawabata
Isao
I
Masakane
Ikuto
I
Suzuki
Takashi
T
Suzuki
Masayuki
M
Goto
Toshikazu
T
Itoh
Kouichi
K
Hayasaka
Kiyoshi
K
D000293:Adolescent; D000328:Adult; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D014598:Uteroglobin / Q000097:blood / Q000235:genetics*
D004247:DNA; D014598:Uteroglobin