Monocyte chemoattractant protein-1 A-2518G gene polymorphism and renal survival of Japanese patients with immunoglobulin A nephropathy.
Monocyte chemoattractant protein-1 A-2518G gene polymorphism and renal survival of Japanese patients with immunoglobulin A nephropathy.
复制标题
DOI：
10.1007/s10157-005-0375-6
复制
发表时间：
2005-12-01
影响因子：
2.3
通讯作者：
Gejyo, Fumitake
中科院分区：
文献类型：
--
作者：
Mori, Honami;Kaneko, Yoshikatsu;Gejyo, Fumitake
背景技术背景：单核细胞趋化蛋白（MCP）-1通过其对巨噬细胞的趋化作用与包括伊加肾病（IgAN）在内的各种慢性肾脏疾病的进展的发病机制密切相关。然而，MCP-1基因多态性与日本IgAN患者长期预后的相关性尚未明确确定。方法：我们调查了277例基于肾活检诊断为IgAN的日本患者，以阐明IgAN进展与MCP-1基因A-2518 G位点多态性之间的关联，该位点调节MCP-1基因的转录。结果：AA基因型患者终末期肾病的发生率（47.1%）显著高于AG（24.1%）或GG（27.4%）基因型患者（P = 0.024）。此外，Kaplan-Meier分析显示AA基因型显著促进肾脏疾病的进展（log rank; P = 0.0029），并且考克斯比例风险回归模型分析显示AA基因型代表与AG/GG基因型相比的2.058倍的肾脏疾病进展风险（P = 0.026）。然而，当患者接受血管紧张素转换酶抑制剂和/或血管紧张素受体阻滞剂或皮质类固醇治疗时，-2518A等位基因的纯合性与终末期肾病的发生率升高无关。具有AA基因型的IgAN患者的血清MCP-1水平较高，但不显着。结论：MCP-1 - 2518的AA基因型是日本IgAN患者肾脏疾病进展的独立危险因素，并且与肾脏密切相关。生存。
BACKGROUND: Monocyte chemoattractant protein (MCP)-1 is closely related to the pathogenesis of the progression of various chronic renal diseases, including IgA nephropathy (IgAN), through its chemoattractant effect on macrophages. However, the correlation of MCP-1 gene polymorphism with the long-term prognosis of Japanese patients with IgAN has not been clearly determined yet.METHODS: We investigated 277 Japanese patients diagnosed with IgAN based on renal biopsy to clarify the association between the progression of IgAN and MCP-1 gene polymorphism at position A-2518G, which regulates the transcription of the MCP-1 gene.RESULTS: The incidence of endstage renal disease was significantly higher in patients with the AA genotype (47.1%) compared to those with the AG (24.1%) or GG (27.4%) genotype (P = 0.024). Moreover, Kaplan-Meier analysis revealed that the AA genotype significantly facilitated the progression of renal disease (log rank; P = 0.0029), and Cox proportional hazards regression model analysis showed that the AA genotype represented a 2.058-fold risk for the progression of renal disease (P = 0.026) compared to the AG/GG genotype. However, when the patients were treated with angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, or corticosteroid, homozygosity for the -2518A allele was not associated with a higher rate of incidence of endstage renal disease. Serum MCP-1 levels were higher although not significantly so, in the patients with IgAN possessing the AA genotype.CONCLUSIONS: The AA genotype at MCP-1 -2518 was an independent risk factor for the progression of renal disease in Japanese patients with IgAN, and was closely associated with renal survival.