Association of the CD14 gene –159C polymorphism with progression of IgA nephropathy
Association of the CD14 gene –159C polymorphism with progression of IgA nephropathy
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DOI：
10.1136/jmg.40.2.104
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发表时间：
2003-02
影响因子：
4
通讯作者：
H. Yoon;J. H. Shin;S. Yang;D. Chae;H. Kim;D.S. Lee;H. Kim;S. Kim;J. S. Lee;Y. Kim
中科院分区：
文献类型：
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作者：
H. Yoon;J. H. Shin;S. Yang;D. Chae;H. Kim;D.S. Lee;H. Kim;S. Kim;J. S. Lee;Y. Kim
伊加肾病（IgAN）是肾小球肾炎的最常见形式，与其进展相关的风险因素尚不清楚。已经表明，响应于各种微生物的CD 14信号传导影响慢性炎性病症的自然史。据推测，CD 14基因启动子区的变异可能会改变CD 14的表达，这反过来又可能影响IgAN的进行性。使用PCR-RFLP确定-159位点（T至C）的多态性。CD 14/−159多态性在IgAN患者（n=216）和171名健康对照者中的分布没有差异。随访86个月后，发现C基因型在疾病进展患者中过量（p=0.03），疾病进展的风险随着C等位基因数量的增加而增加（趋势p = 0.002）。与TT基因型患者相比，CC基因型患者进展的风险比为3.2（p=0.025）。LPS刺激后，sCD 14从TT受试者的PBMC中释放的量比CC受试者的PBMC中释放的量多（p=0.006），尽管mCD 14表达水平没有差异。此外，TT受试者在刺激后释放的IL-6少于CC受试者（p=0.0003）。这些结果表明，CD 14/−159多态性是IgAN进展的重要标志物，并可能调节炎症反应的水平。
The risk factors associated with the progression of IgA nephropathy (IgAN), the most common form of glomerulonephritis, are unclear. It has been suggested that CD14 signalling in response to various microbes affects the natural history of chronic inflammatory conditions. It has been hypothesised that variants in the promoter region of the CD14 gene might alter the expression of CD14, and this in turn could influence the progressive nature of IgAN. PCR-RFLP was used to determine the polymorphism at the −159 site (T to C). The distribution of the CD14/−159 polymorphism was no different in patients with IgAN (n=216) compared to 171 healthy controls. After follow up for 86 months, it was found that an excess of the C genotype occurred in patients with progressive disease (p=0.03) and the risk of disease progression increased as the number of C alleles increased (p for trend = 0.002). The hazard ratio for progression in the patients with the CC genotype was 3.2 (p=0.025) compared with the patients possessing the TT genotype. After LPS stimulation, sCD14 was released more abundantly from the PBMCs of the TT subjects than from that of the CC subjects (p=0.006), even though mCD14 expression level was no different. In addition, the TT subjects released less IL-6 than the CC subjects after stimulation (p=0.0003). These results suggest that the CD14/−159 polymorphism is an important marker for the progression of IgAN and may modulate the level of the inflammatory responses.