Frontiers in Nutrition (Apr 2022)

Genetic Evidence Supporting the Causal Role of Homocysteine in Chronic Kidney Disease: A Mendelian Randomization Study

  • Yang Xiong,
  • Yang Xiong,
  • Yangchang Zhang,
  • Fuxun Zhang,
  • Fuxun Zhang,
  • Changjing Wu,
  • Peiyi Luo,
  • Feng Qin,
  • Jiuhong Yuan,
  • Jiuhong Yuan

DOI
https://doi.org/10.3389/fnut.2022.843534
Journal volume & issue
Vol. 9

Abstract

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BackgroundThe causal relationship between homocysteine (Hcy) levels and chronic kidney disease (CKD) remains unclear. This study was performed to estimate the potential causal effects of Hcy on the estimated glomerular filtration rate (eGFR) and CKD.Materials and MethodsThe single nucleotide polymorphisms (SNPs) associated with one standard deviation (SD) Hcy increase were identified using the genome-wide association study (GWAS). The summary statistics of the eGFR and CKD were from the CKDGen project in the European ancestry and the Population Architecture using Genomics and Epidemiology (PAGE) project in the non-European ancestry. Two-sample Mendelian randomization (MR) analyses were used in this study to verify the causal effects among Hcy, eGFR, and CKD.ResultsThe results showed that 1-SD Hcy increase was causally associated with eGFR decline in the CKDGen project (β = −0.027 log ml.min–1/1.73 m2, p < 0.01 for the overall cohort; β = −0.028 log ml.min–1/1.73 m2, p < 0.01 after excluding the patients with diabetes). In addition, 1-SD Hcy increase was associated with a 1.32-fold risk of CKD in the PAGE project (95% CI = 1.06–1.64, p < 0.05). The association was directionally similar in the CKDGen project [odds ratio (OR) = 1.08, 95% CI = 0.97–1.44, p = 0.098]. The pooled OR of CKD was 1.24 (95% CI = 1.07–1.44, p < 0.05) per 1-SD Hcy increase.ConclusionUsing genetic data, Hcy increase is causally associated with renal function injury and further CKD.

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