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Abstract：
Inflammation has been associated with renal diseases. The Interferon Regulatory Factor (IRF)-5 is a key transcription factor in the pro-inflammatory polarization of M1-like macrophages. GWAS have reported that the IRF5 locus is associated with autoimmune diseases and with the estimated glomerular filtration rate (eGFR). We study whether allelic variations in IRF5 are associated with the incidence of chronic kidney disease (CKD) in a general population. We genotyped eleven IRF5 SNPs in the French D.E.S.I.R. cohort from the general population (n = 4820). Associations of SNPs with baseline renal parameters were assessed. Data were analyzed for three endpoints during a 9-year follow-up, incidence of:at least stage 3 CKD, the KDIGO criterion \"certain drop in eGFR\", and incidence of micro/macro albuminuria. In the cross-sectional analysis, rs10954213 and rs10954214 were associated with eGFR and rs1874328 with urinary albumin/creatinine ratio (ACR). Rs3807306, rs11761199, rs78658945, rs1874328, rs10954213 and rs11770589 were associated with the incidence of stage 3 CKD in multi-adjusted models. Rs4731532, rs3807306, and rs11761199 were associated with the incidence of CKD defined by the KDIGO. Rs4731532, rs3807306, rs11761199 and rs79288514 were associated with the incidence of micro/macro albuminuria. Our results support the hypothesis of the importance of IRF5 mediated macrophage polarization in the etiology of CKD.
摘要：
炎症与肾脏疾病相关。干扰素调节因子（IRF）-5是M1样巨噬细胞促炎极化的关键转录因子。GWAS已经报道IRF5基因座与自身免疫性疾病和估计的肾小球滤过率(eGFR)相关。我们研究了IRF5的等位基因变异是否与普通人群中慢性肾脏病（CKD）的发病率相关。我们对来自普通人群的法国D.E.S.I.R.队列中的11个IRF5SNP进行了基因分型(n=4820)。评估SNP与基线肾脏参数的关联。在9年的随访中分析了三个终点的数据，发病率：至少3期CKD，KDIGO标准“eGFR的一定下降”，和微/宏白蛋白尿的发生率。在横截面分析中，rs10954213和rs10954214与eGFR和rs1874328与尿白蛋白/肌酐比值（ACR）相关。rs3807306，rs11761199，rs78658945，rs1874328，rs10954213和rs11770589与多调整模型中3期CKD的发生率相关。rs4731532、rs3807306和rs11761199与KDIGO定义的CKD发病率相关。rs4731532，rs3807306，rs11761199和rs79288514与微/宏白蛋白尿的发生率相关。我们的结果支持IRF5介导的巨噬细胞极化在CKD病因中重要性的假设。
