Analysis of SNPs and pathogenesis of human Protein 1 gene

人类Protein 1基因SNP及发病机制分析

• 批准号: 13672411
• 负责人: KAWABATA Isao
• 金额: $ 1.6万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672411/
• 关键词: CC10; uteroglobin; IgA nephropathy; SNPs; interferon-gamma; sarcoidosis; サルコイドーシス; IgA腎症; SNP; Single Nucleotide Polymorphisms; IgA Nephropathy

Clara cell 10-kDa protein (CC10)/uteroglobin (UG) is a nonglycoprotein with a molecular mass of 16 kilodaltons, which is produced by mucosal epithelial cells in the lung (Clara cells), uterus and prostate.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.The value is changed in the lung fluid and serum of various inflammatory and allergic lung diseases. Several kinds of single nucleotide polymorphisms (SNPs) in human CC10/UG gene were recently discovered ; Adenine allele accumulation in G38A SNP has possible association with asthma and IgA nephropathy, being paralleled with disease severity of IgA nephropathy. Its expression is enhanced by some transcriptional factors induced by cytokines such as interferon-gamma. For cancer cells, the protein functions as an antagonist of neoplastic phenotype.We also analyzed the expression of uteroglobin in 15 menopausal women who received hormone replacement therapy (HRT). The expression of uteroglobin was higher during the secretory phase than in the proliferative phase, however, it was detected in endometrial hyperplasia as weakly as in the proliferative phase and decreased according to the loss of differentiation in endometrial carcinoma.

Clara 细胞 10-kDa 蛋白 (CC10)/子宫珠蛋白 (UG) 是一种分子量为 16 千道尔顿的非糖蛋白，由肺（Clara 细胞）、子宫和前列腺中的粘膜上皮细胞产生。我们对 UG 基因进行了分析：在 61 名日本 IgA 肾病患者（23 名儿童，38 名成人）中寻找诱发因素的候选者，仅检测到 G38A 突变。患者的G38A突变基因频率为0.43，与健康对照的0.36频率没有显着差异。然而，G38A纯合子患者的频率是对照组的两倍，并且在儿童患者中显着增加。我们测量了患者和健康成人的血清 UG 水平。与G38纯合子相比，仅在成年女性患者和对照中检测到G38A纯合子的血清UG水平显着降低。该值在各种炎症和过敏性肺部疾病的肺液和血清中发生变化。最近在人类CC10/UG基因中发现了多种单核苷酸多态性(SNP)； G38A SNP 中的腺嘌呤等位基因积累可能与哮喘和 IgA 肾病相关，并且与 IgA 肾病的疾病严重程度平行。其表达可通过细胞因子（例如干扰素-γ）诱导的一些转录因子增强。对于癌细胞，该蛋白起到肿瘤表型拮抗剂的作用。我们还分析了 15 名接受激素替代疗法 (HRT) 的绝经期妇女的子宫珠蛋白表达。子宫珠蛋白的表达在分泌期高于增殖期，但在子宫内膜增生期的表达与增殖期一样弱，并且在子宫内膜癌中随着分化的丧失而减少。

项目成果

四十坊典晴: "クララ10kDa蛋白質"臨床化学. 32巻. 227-233 (2003)

Noriharu Yosobo：“Clara 10kDa 蛋白质”临床化学卷 32. 227-233 (2003)

河端 薫雄: "遺伝子検査によるオーダーメイド医療"臨床病理. Vol.50 No.12. 1124-1129 (2002)

Kaoru Kawabata：“通过基因检测进行个性化医疗”《临床病理学》第 50 卷第 1124-1129 期（2002 年）。

河端 薫雄: "遺伝子検査によるオーダーメイド医療"臨床病理. Vol.50. 1124-1129 (2002)

Kaoru Kawabata：“通过基因检测进行个性化医疗”《临床病理学》第 50 卷（2002 年）。

Ohchi T, Shijubo N, Kawabata I, Ichimiya S, Inomata S, Yamaguchi A, Umemori Y. Itoh Y, Abe S. Hiraga Y. Sato N.: "Polymorphism of Clara cell 10-kD protein gene of sarcoidosis"Am J Rcspir Cnt Care Med.(Jan 15 Epub 2003 Oct 09). 169(2). 180-186 (2003)

Ohchi T、Shijubo N、Kawabata I、Ichimiya S、Inomata S、Yamaguchi A、Umemori Y. Itoh Y、Abe S. Hiraga Y. Sato N.：“结节病的 Clara 细胞 10-kD 蛋白基因的多态性”Am J Rcspir

Shijubo N.: "Clinical aspects of Clara cell 10-kDa protein/uteroglobin(secretoglobin 1A1)."Curr Pharm Des.. Vol.9. (2003)

Shijubo N.：“Clara 细胞 10-kDa 蛋白/子宫珠蛋白（分泌珠蛋白 1A1）的临床方面。”Curr Pharm Des.. 第 9 卷。