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

BACKGROUND: The 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 METHODS: The single nucleotide po...

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Autores principales: Xiong, Yang, Zhang, Yangchang, Zhang, Fuxun, Wu, Changjing, Luo, Peiyi, Qin, Feng, Yuan, Jiuhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9048023/
https://www.ncbi.nlm.nih.gov/pubmed/35495913
http://dx.doi.org/10.3389/fnut.2022.843534
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author Xiong, Yang
Zhang, Yangchang
Zhang, Fuxun
Wu, Changjing
Luo, Peiyi
Qin, Feng
Yuan, Jiuhong
author_facet Xiong, Yang
Zhang, Yangchang
Zhang, Fuxun
Wu, Changjing
Luo, Peiyi
Qin, Feng
Yuan, Jiuhong
author_sort Xiong, Yang
collection PubMed
description BACKGROUND: The 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 METHODS: The 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. RESULTS: The 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 m(2), p < 0.01 for the overall cohort; β = −0.028 log ml.min(–1)/1.73 m(2), 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. CONCLUSION: Using genetic data, Hcy increase is causally associated with renal function injury and further CKD.
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spelling pubmed-90480232022-04-29 Genetic Evidence Supporting the Causal Role of Homocysteine in Chronic Kidney Disease: A Mendelian Randomization Study Xiong, Yang Zhang, Yangchang Zhang, Fuxun Wu, Changjing Luo, Peiyi Qin, Feng Yuan, Jiuhong Front Nutr Nutrition BACKGROUND: The 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 METHODS: The 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. RESULTS: The 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 m(2), p < 0.01 for the overall cohort; β = −0.028 log ml.min(–1)/1.73 m(2), 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. CONCLUSION: Using genetic data, Hcy increase is causally associated with renal function injury and further CKD. Frontiers Media S.A. 2022-04-14 /pmc/articles/PMC9048023/ /pubmed/35495913 http://dx.doi.org/10.3389/fnut.2022.843534 Text en Copyright © 2022 Xiong, Zhang, Zhang, Wu, Luo, Qin and Yuan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Xiong, Yang
Zhang, Yangchang
Zhang, Fuxun
Wu, Changjing
Luo, Peiyi
Qin, Feng
Yuan, Jiuhong
Genetic Evidence Supporting the Causal Role of Homocysteine in Chronic Kidney Disease: A Mendelian Randomization Study
title Genetic Evidence Supporting the Causal Role of Homocysteine in Chronic Kidney Disease: A Mendelian Randomization Study
title_full Genetic Evidence Supporting the Causal Role of Homocysteine in Chronic Kidney Disease: A Mendelian Randomization Study
title_fullStr Genetic Evidence Supporting the Causal Role of Homocysteine in Chronic Kidney Disease: A Mendelian Randomization Study
title_full_unstemmed Genetic Evidence Supporting the Causal Role of Homocysteine in Chronic Kidney Disease: A Mendelian Randomization Study
title_short Genetic Evidence Supporting the Causal Role of Homocysteine in Chronic Kidney Disease: A Mendelian Randomization Study
title_sort genetic evidence supporting the causal role of homocysteine in chronic kidney disease: a mendelian randomization study
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9048023/
https://www.ncbi.nlm.nih.gov/pubmed/35495913
http://dx.doi.org/10.3389/fnut.2022.843534
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