Molecular Epidemiology and Public Health Research Group, Centre for Public Health, Queen's University Belfast, Institute for Clinical Sciences A, Royal Victoria Hospital, Belfast BT12 6BA, UK.
Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer-University of Granada-Andalusian Regional Government, PTS Granada, Avenida de la Ilustración 114, 18016 Granada, Spain.
Int J Mol Sci. 2023 Jul 7;24(13):11209. doi: 10.3390/ijms241311209.
Increased albuminuria indicates underlying glomerular pathology and is associated with worse renal disease outcomes, especially in diabetic kidney disease. Many single nucleotide polymorphisms (SNPs), associated with albuminuria, could be potentially useful to construct polygenic risk scores (PRSs) for kidney disease. We investigated the diagnostic accuracy of SNPs, previously associated with albuminuria-related traits, on albuminuria and renal injury in the UK Biobank population, with a particular interest in diabetes. Multivariable logistic regression was used to evaluate the influence of 91 SNPs on urine albumin-to-creatinine ratio (UACR)-related traits and kidney damage (any pathology indicating renal injury), stratifying by diabetes. Weighted PRSs for microalbuminuria and UACR from previous studies were used to calculate the area under the receiver operating characteristic curve (AUROC). -rs1801239 and -rs116772905 were associated with all the UACR-derived phenotypes, in both the overall and non-diabetic cohorts, but not with kidney damage. Several SNPs demonstrated different effects in individuals with diabetes compared to those without. SNPs did not improve the AUROC over currently used clinical variables. Many SNPs are associated with UACR or renal injury, suggesting a role in kidney dysfunction, dependent on the presence of diabetes in some cases. However, individual SNPs or PRSs did not improve the diagnostic accuracy for albuminuria or renal injury compared to standard clinical variables.
尿白蛋白升高表明存在肾小球病变，并与肾脏疾病不良结局相关，尤其在糖尿病肾病中。许多与白蛋白尿相关的单核苷酸多态性（SNP）可用于构建多基因风险评分（PRS）来预测肾脏疾病。我们在英国生物库人群中研究了先前与白蛋白尿相关特征相关的 SNP 对白蛋白尿和肾脏损伤的诊断准确性，特别关注糖尿病。多变量逻辑回归用于评估 91 个 SNP 对尿白蛋白/肌酐比值（UACR）相关特征和肾脏损伤（任何表明肾脏损伤的病理）的影响，按糖尿病分层。使用先前研究的微白蛋白尿和 UACR 的加权 PRS 来计算受试者工作特征曲线下的面积（AUROC）。-rs1801239 和 -rs116772905 与总体和非糖尿病队列中所有 UACR 衍生表型相关，但与肾脏损伤无关。与非糖尿病患者相比，一些 SNP 在糖尿病患者中表现出不同的作用。SNP 并未提高目前使用的临床变量的 AUROC。许多 SNP 与 UACR 或肾脏损伤相关，这表明在某些情况下，它们在肾脏功能障碍中起作用，取决于糖尿病的存在。然而，与标准临床变量相比，单个 SNP 或 PRS 并未提高白蛋白尿或肾脏损伤的诊断准确性。
