■糖尿病是全球最普遍的疾病之一,肾脏特别容易受到血管并发症的影响。鉴定蛋白质的发病机理和新的药物靶标仍然是当务之急。本研究旨在探讨循环炎症蛋白在糖尿病肾脏并发症中的作用。
■蛋白质的数据来自全基因组蛋白质数量性状基因座(pQTL)研究,而糖尿病肾脏并发症的数据来自FinnGen研究。在这项研究中,本研究采用全蛋白质组孟德尔随机化(MR)和共定位分析评估循环炎症蛋白与糖尿病肾脏并发症之间的关系.
■MR方法表明,白细胞介素12B(IL-12B)(OR1.691,95CI1.179-2.427,P=4.34×10-3)和LIF白细胞介素6家族细胞因子(LIF)(OR1.349,95CI1.010-1.801,P=4.23×10-2)水平升高增加了1型糖尿病(T1D)合并肾脏并发症的风险,而较高水平的成纤维细胞生长因子19(FGF19)(OR1.202,95CI1.009-1.432,P=3.93×10-2),成纤维细胞生长因子23(FGF23)(OR1.379,95CI1.035-1.837,P=2.82×10-2),C-C基序趋化因子配体7(CCL7)(OR1.385,95CI1.111-1.725,P=3.76×10-3),TNF超家族成员14(TNFSF14)(OR1.244,95CI1.066-1.451,P=5.63×10-3)表明2型糖尿病(T2D)合并肾脏并发症的潜在危险因素。协同定位分析支持了这些发现,揭示了大多数鉴定的蛋白质,除了DNER,可能与糖尿病肾脏并发症有共同的因果变异。
■我们的研究建立了特定循环炎症蛋白与糖尿病肾脏并发症风险之间的关联,提示这些蛋白质可作为进一步研究T1D和T2D合并肾脏并发症的发病机制和潜在治疗干预措施的靶标。
UNASSIGNED: Diabetes ranks among the most widespread diseases globally, with the kidneys being particularly susceptible to its vascular complications. The identification of proteins for pathogenesis and novel drug targets remains imperative. This study aims to investigate roles of circulating inflammatory proteins in diabetic renal complications.
UNASSIGNED: Data on the proteins were derived from a genome-wide protein quantitative trait locus (pQTL) study, while data on diabetic renal complications came from the FinnGen study. In this study, proteome-wide Mendelian randomization (MR) and colocalization analyses were used to assess the relationship between circulating inflammatory proteins and diabetic renal complications.
UNASSIGNED: MR approach indicated that elevated levels of interleukin 12B (IL-12B) (OR 1.691, 95%CI 1.179-2.427, P=4.34×10-3) and LIF interleukin 6 family cytokine (LIF) (OR 1.349, 95%CI 1.010-1.801, P=4.23×10-2) increased the risk of type 1 diabetes (T1D) with renal complications, while higher levels of fibroblast growth factor 19 (FGF19) (OR 1.202, 95%CI 1.009-1.432, P=3.93×10-2), fibroblast growth factor 23 (FGF23) (OR 1.379, 95%CI 1.035-1.837, P=2.82×10-2), C-C motif chemokine ligand 7 (CCL7) (OR 1.385, 95%CI 1.111-1.725, P=3.76×10-3), and TNF superfamily member 14 (TNFSF14) (OR 1.244, 95%CI 1.066-1.451, P=5.63×10-3) indicated potential risk factors for type 2 diabetes (T2D) with renal complications. Colocalization analysis supported these findings, revealing that most identified proteins, except for DNER, likely share causal variants with diabetic renal complications.
UNASSIGNED: Our study established associations between specific circulating inflammatory proteins and the risk of diabetic renal complications, suggesting these proteins as targets for further investigation into the pathogenesis and potential therapeutic interventions for T1D and T2D with renal complications.