Matsunaga Akira, Numakura Chikahiko, Kawakami Takako, Itoh Yoshihisa, Kawabata Isao, Masakane Ikuto, Suzuki Takashi, Suzuki Masayuki, Goto Toshikazu, Itoh Kouichi, Hayasaka Kiyoshi
Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
Am J Kidney Dis. 2002 Jan;39(1):36-41. doi: 10.1053/ajkd.2002.29875.
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.
免疫球蛋白A（IgA）肾病是由IgA在肾系膜中的异常沉积所致。遗传因素可能参与IgA肾病的发生和发展。子宫珠蛋白（UG）是一种类固醇诱导的、细胞因子样的多功能蛋白，具有抗炎和免疫调节特性。UG基因敲除或反义小鼠会发生类似于IgA肾病的肾脏疾病。我们分析了UG基因作为61例日本IgA肾病患者（23例儿童，38例成人）易感因素的可能性，仅检测到G38A突变。患者中G38A突变的基因频率为0.43，与健康对照者0.36的频率无显著差异。然而，G38A纯合子患者的频率是对照者的两倍，且在儿童患者中显著增加。我们测量了患者和健康成年人的血清UG水平。仅在成年女性患者和对照者中检测到，与G38纯合子相比，G38A纯合子的血清UG水平显著降低。目前尚无关于血清UG产生部位或UG如何与IgA肾病相关起作用的信息。然而，G38A的影响可能在诸如性类固醇或感染等刺激下变得明显，且G38A突变的纯合子在受到刺激时无法产生足够的UG，可能易患IgA肾病，尤其是在儿童期。
