在基于人群的KORA F4研究中，血清尿调节蛋白与亚临床炎症生物标志物呈负相关。
Serum uromodulin is inversely associated with biomarkers of subclinical inflammation in the population-based KORA F4 study.
作者信息
Then Cornelia, Herder Christian, Then Holger, Thorand Barbara, Huth Cornelia, Heier Margit, Meisinger Christa, Peters Annette, Koenig Wolfgang, Rathmann Wolfgang, Roden Michael, Stumvoll Michael, Maalmi Haifa, Meitinger Thomas, Lechner Andreas, Scherberich Jürgen, Seissler Jochen
机构信息
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU, München, Germany.
Clinical Cooperation Group Diabetes, Ludwig-Maximilians-Universität München and Helmholtz Zentrum München, Munich, Germany.
出版信息
Clin Kidney J. 2020 Sep 6;14(6):1618-1625. doi: 10.1093/ckj/sfaa165. eCollection 2021 Jun.
BACKGROUND
Uromodulin is a kidney-specific glycoprotein synthesized in tubular cells of Henle's loop exerting nephroprotective and immunomodulatory functions in the urinary tract. A small amount of uromodulin is also released into the systemic circulation, where its physiological role is unknown. Serum uromodulin (sUmod) has been associated with metabolic risk factors and with cardiovascular events and mortality, where these associations were partly stronger in men than in women. In this study, we investigated the associations of sUmod with biomarkers of subclinical inflammation in a population-based sample of women and men.
METHODS
Associations of sUmod with 10 biomarkers of subclinical inflammation were assessed in 1065 participants of the Cooperative Health Research in the Region of Augsburg (KORA) F4 study aged 62-81 years using linear regression models adjusted for sex, age, body mass index, estimated glomerular filtration rate and diabetes. Analyses were performed in the total study sample and stratified by sex.
RESULTS
sUmod was inversely associated with white blood cell count, high-sensitive C-reactive protein, interleukin (IL)-6, tumour necrosis factor-α, myeloperoxidase, superoxide dismutase-3, IL-1 receptor antagonist and IL-22 after multivariable adjustment and correction for multiple testing (P < 0.001 for each observation). There was a trend towards a stronger association of sUmod with pro-inflammatory markers in men than in women, with a significant P for sex interaction (<0.001) regarding the relation of sUmod with IL-6.
CONCLUSIONS
sUmod was inversely associated with biomarkers of subclinical inflammation in older participants of the KORA F4 study. The association of sUmod with IL-6 differed between women and men. Future research should focus on whether the immunomodulatory properties of sUmod are one explanation for the association of sUmod with cardiovascular outcomes and mortality.
背景
尿调节蛋白是一种肾脏特异性糖蛋白，在髓袢肾小管细胞中合成，在尿路发挥肾保护和免疫调节功能。少量尿调节蛋白也释放到体循环中，其生理作用尚不清楚。血清尿调节蛋白（sUmod）与代谢危险因素、心血管事件及死亡率相关，且这些关联在男性中部分比女性更强。在本研究中，我们在一个基于人群的男女样本中调查了sUmod与亚临床炎症生物标志物的关联。
方法
在奥格斯堡地区合作健康研究（KORA）F4研究的1065名年龄在62 - 81岁的参与者中，使用针对性别、年龄、体重指数、估计肾小球滤过率和糖尿病进行调整的线性回归模型，评估sUmod与10种亚临床炎症生物标志物的关联。分析在整个研究样本中进行，并按性别分层。
结果
经过多变量调整和多重检验校正后，sUmod与白细胞计数、高敏C反应蛋白、白细胞介素（IL）-6、肿瘤坏死因子-α、髓过氧化物酶、超氧化物歧化酶-3、IL-1受体拮抗剂和IL-22呈负相关（每项观察P < 0.001）。sUmod与促炎标志物的关联在男性中比在女性中更强，关于sUmod与IL-6的关系，性别交互作用有显著P值（<0.001）。
结论
在KORA F4研究的老年参与者中，sUmod与亚临床炎症生物标志物呈负相关。sUmod与IL-6的关联在女性和男性中有所不同。未来的研究应关注sUmod的免疫调节特性是否是其与心血管结局及死亡率关联的一种解释。
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