2 型糖尿病/慢性肾脏病遗传风险评分与 2 型糖尿病患者糖尿病肾脏疾病的进展。

T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects.

机构信息

Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Biochemistry, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

出版信息

Gene. 2024 Nov 15;927:148724. doi: 10.1016/j.gene.2024.148724. Epub 2024 Jun 22.

Abstract

This study aimed at understanding the predictive potential of genetic risk scores (GRS) for diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM) and Major Cardiovascular Events (MCVE) and All-Cause Mortality (ACM) as secondary outcomes. We evaluated 30 T2DM and CKD GWAS-derived single nucleotide polymorphisms (SNPs) and their association with clinical outcomes in a central European cohort (n = 400 patients). Our univariate Cox analysis revealed significant associations of age, duration of diabetes, diastolic blood pressure, total cholesterol and eGFR with progression of DKD (all P < 0.05). However, no single SNP was conclusively associated with progression to DKD, with only CERS2 and SHROOM3 approaching statistical significance. While a single SNP was associated with MCVE - WSF1 (P = 0.029), several variants were associated with ACM - specifically CANCAS1, CERS2 and C9 (all P < 0.02). Our GRS did not outperform classical clinical factors in predicting progression to DKD, MCVE or ACM. More precisely, we observed an increase only in the area under the curve (AUC) in the model combining genetic and clinical factors compared to the clinical model alone, with values of 0.582 (95 % CI 0.487-0.676) and 0.645 (95 % CI 0.556-0.735), respectively. However, this difference did not reach statistical significance (P = 0.06). This study highlights the complexity of genetic predictors and their interplay with clinical factors in DKD progression. Despite the promise of personalised medicine through genetic markers, our findings suggest that current clinical factors remain paramount in the prediction of DKD. In conclusion, our results indicate that GWAS-derived GRSs for T2DM and CKD do not offer improved predictive ability over traditional clinical factors in the studied Czech T2DM population.

摘要

本研究旨在探讨遗传风险评分(GRS)对 2 型糖尿病(T2DM)合并大血管事件(MCVE)和全因死亡率(ACM)的患者糖尿病肾病(DKD)进展的预测潜力,将其作为次要结局。我们评估了来自 30 个 T2DM 和 CKD GWAS 的单核苷酸多态性(SNP)及其与中欧队列(n=400 例患者)临床结局的关联。我们的单变量 Cox 分析显示,年龄、糖尿病病程、舒张压、总胆固醇和 eGFR 与 DKD 进展显著相关(均 P<0.05)。然而,没有单个 SNP 与 DKD 进展有明确关联,只有 CERS2 和 SHROOM3 接近统计学意义。虽然单个 SNP 与 MCVE 相关-WSF1(P=0.029),但多个变体与 ACM 相关-特别是 CANCAS1、CERS2 和 C9(均 P<0.02)。我们的 GRS 在预测 DKD、MCVE 或 ACM 进展方面并不优于传统临床因素。更确切地说,我们观察到与仅临床模型相比,在结合遗传和临床因素的模型中,曲线下面积(AUC)仅略有增加,分别为 0.582(95%CI 0.487-0.676)和 0.645(95%CI 0.556-0.735)。然而,这一差异没有达到统计学意义(P=0.06)。本研究强调了遗传预测因子的复杂性及其与 DKD 进展中临床因素的相互作用。尽管通过遗传标志物实现个体化医疗具有前景,但我们的研究结果表明,当前的临床因素在预测 DKD 方面仍然至关重要。总之,我们的研究结果表明,在研究的捷克 T2DM 人群中,GWAS 衍生的 T2DM 和 CKD GRS 并没有比传统临床因素提供更好的预测能力。

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