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西班牙RENASTUR队列中IL17RA基因rs4819554多态性与肾滤过率降低之间的关联。

Association between the IL17RA rs4819554 polymorphism and reduced renal filtration rate in the Spanish RENASTUR cohort.

作者信息

Coto Eliecer, Gómez Juan, Suárez Beatriz, Tranche Salvador, Díaz-Corte Carmen, Ortiz Alberto, Ruiz-Ortega Marta, Coto-Segura Pablo, Batalla Ana, López-Larrea Carlos

机构信息

Genética Molecular-Laboratorio Medicina, HUCA, Oviedo, Spain; Red de Investigación Renal - Instituto Salud Carlo III, Madrid, Spain; Fundación Renal I. Alvarez de Toledo, Madrid, Spain.

Genética Molecular-Laboratorio Medicina, HUCA, Oviedo, Spain.

出版信息

Hum Immunol. 2015 Mar;76(2-3):75-8. doi: 10.1016/j.humimm.2015.01.027. Epub 2015 Jan 27.

Abstract

DNA variants at the genes that encode components of the IL17-pathway may contribute to the risk of impaired renal function/chronic kidney disease. Our aim was to determine whether common IL17RA single nucleotide polymorphisms (SNPs) were associated with a reduced estimated glomerular filtration rate (eGFR) in a cohort of healthy elderly individuals (n=650). We found a significantly higher frequency of SNP rs4819554 AA homozygotes among individuals with eGFR<60 ml/min/1.73 m(2) (n=90) (p=0.005, OR=2.11; 1.26-3.54), an effect that was independent of the presence of type 2 diabetes. Allele rs4819554 A had been associated to the risk of developing end stage renal disease, and was also linked to an increased expression of the IL17RA protein and higher levels of Th17 cell subsets. A scenario in which the pro-inflammatory role of the IL17-pathway contributes to kidney damage might explain the association between Il17RA polymorphisms and an impaired renal function.

摘要

编码白细胞介素17(IL17)信号通路成分的基因中的DNA变异可能会增加肾功能受损/慢性肾病的风险。我们的目的是确定常见的白细胞介素17受体A(IL17RA)单核苷酸多态性(SNP)是否与一组健康老年人(n = 650)的估计肾小球滤过率(eGFR)降低有关。我们发现,在eGFR<60 ml/min/1.73 m²的个体(n = 90)中,SNP rs4819554 AA纯合子的频率显著更高(p = 0.005,OR = 2.11;1.26 - 3.54),这一效应独立于2型糖尿病的存在。等位基因rs4819554 A与终末期肾病的发生风险相关,并且还与IL17RA蛋白表达增加和Th17细胞亚群水平升高有关。IL17信号通路的促炎作用导致肾脏损伤的情况可能解释了IL17RA多态性与肾功能受损之间的关联。

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