Impact of lifetime concentration of mannose on renal function: insights from Mendelian randomization. (3rd October 2022)

• Record Type: Journal Article
• Authors: Mazidi, M; Shekoohi, N; Katsiki, N; Banach, M
• Is Part Of: European heart journal. Volume 43(2022)Supplement 2
• Publication Date: 2022-10-03
• Subjects: Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehac544.2612
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Background: Mannose is a sugar monomer of the aldohexose series of carbohydrates, important in human metabolism, especially in the glycosylation of certain proteins. There is a handful of controversial data from observational studies on the serum levels of mannose and risks of renal disease. Purpose: We performed a Mendelian Randomization (MR) analysis to obtain unconfounded estimates of the casual associations between genetically instrumented serum mannose, estimated glomerular filtration rate (eGFR) and the risk for chronic kidney disease (CKD defined as eGFR <60 ml/min/1.73 m 2 ). Methods: MR was implemented by using summary-level data from the largest ever genome-wide association studies (GWAS) conducted on serum mannose and renal function. Inverse variance weighted method (IVW), weighted median (WM)-based method, MR-Egger, MR-Robust Adjusted Profile Score (RAPS), MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were also applied. Sensitivity analysis was conducted using the leave-one-out method. The analyses were performed in the total population, in non-diabetics and in patients with type 2 diabetes mellitus (T2DM). Results: Serum mannose concentrations were not significantly associated with CKD risk (IVW: beta=1.018, p=0.273), but they were negatively related to eGFR in the total population (IVW: beta=−0.137, p=0.003), the non-diabetics (IVW: beta=−0.126, p=0.018) and the T2DM patients (IVW: beta=−0.344, p=0.004). None of the MR-Egger estimates showed heterogeneity, and the MR-PRESSO analysis did not find any possibility of outliers for all of the estimates. The pleiotropy test also indicated a low chance of pleiotropy for all estimations (p>0.242), as did the MR-RAPS analysis. Leave-one-out method demonstrated that the observed associations were not driven by single-nucleotide polymorphisms. Conclusions: Our results highlighted that individuals with genetically higher serum mannose levels have a significantly lower eGFR, regardless of the presence or absence of T2DM. However, no association between serum mannose concentrations and the risk of CKD was observed. Funding Acknowledgement: Type of funding sources: None.