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Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end‐stage renal disease

BACKGROUND: MicroRNA (miRNA) processing machinery gene variant was associated with several diseases. We aimed to explore for the first time the association of machinery gene (DROSHA rs10719A/G; DICER1 rs3742330A/G; RAN rs14035C/T; and XPO5 rs11077T/G) variants with the susceptibility and phenotype o...

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Autores principales: Fawzy, Manal S., Abu AlSel, Baraah T., Toraih, Eman A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755820/
https://www.ncbi.nlm.nih.gov/pubmed/32770606
http://dx.doi.org/10.1002/jcla.23520
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author Fawzy, Manal S.
Abu AlSel, Baraah T.
Toraih, Eman A.
author_facet Fawzy, Manal S.
Abu AlSel, Baraah T.
Toraih, Eman A.
author_sort Fawzy, Manal S.
collection PubMed
description BACKGROUND: MicroRNA (miRNA) processing machinery gene variant was associated with several diseases. We aimed to explore for the first time the association of machinery gene (DROSHA rs10719A/G; DICER1 rs3742330A/G; RAN rs14035C/T; and XPO5 rs11077T/G) variants with the susceptibility and phenotype of end‐stage renal disease (ESRD). METHOD: A total of 281 participants (98 ESRD patients and 183 healthy volunteers) were enrolled. Real‐Time TaqMan allelic discrimination assay was applied for the genotyping of the specified variants. Multiple logistic regression models, univariate, multivariate, and principal component analyses were carried out. RESULTS: Carrying one DICER1 rs3742330*G allele conferred protection against developing ESRD [heterozygote comparison: OR = 0.30, 95% CI = 0.15‐0.62, dominant model: OR = 0.35, 95% CI = 0.17‐0.70]. Similarly, for XPO5 rs11077T/G, homozygote and heterozygote carriers of G variant were less likely to develop ESRD [homozygote comparison: adjusted OR = 0.23, 95% CI = 0.11‐0.50, and heterozygote comparison: OR = 0.50, 95% CI = 0.22‐0.92, and allelic model: OR = 0.46, 95% CI = 0.34‐0.70]. RAN rs14035*TT subjects were 5 times more likely to develop ESRD while being heterozygote (CT) have twice the risk [homozygote comparison: 5.18, 95% CI = 2.28‐11.8, heterozygote comparison: OR = 2.12, 95% CI = 1.10‐409]. Subgroup analysis also detected DICER1 rs3742330*A, XPO5 rs11077*T, and RAN rs14035*T as genetic risk determinants for ESRD development in both sex and age categories. Two genotype combinations of DROSHA/DICER1/XPO5/RAN were associated with increased susceptibility to ESRD [A‐A‐T‐T: OR = 9.49, 95%CI = 2.48‐36.31 (P = .001) and G‐A‐T‐T: OR = 5.92, 95%CI = 1.77‐19.83 (P = .004), respectively]. CONCLUSION: Variants and combined genotypes of DICER1 rs3742330, XPO5 rs11077, and RAN rs14035 might be associated with ESRD development in the study population. Integrating molecular analysis in ESRD risk stratification is warranted.
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spelling pubmed-77558202020-12-23 Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end‐stage renal disease Fawzy, Manal S. Abu AlSel, Baraah T. Toraih, Eman A. J Clin Lab Anal Research Articles BACKGROUND: MicroRNA (miRNA) processing machinery gene variant was associated with several diseases. We aimed to explore for the first time the association of machinery gene (DROSHA rs10719A/G; DICER1 rs3742330A/G; RAN rs14035C/T; and XPO5 rs11077T/G) variants with the susceptibility and phenotype of end‐stage renal disease (ESRD). METHOD: A total of 281 participants (98 ESRD patients and 183 healthy volunteers) were enrolled. Real‐Time TaqMan allelic discrimination assay was applied for the genotyping of the specified variants. Multiple logistic regression models, univariate, multivariate, and principal component analyses were carried out. RESULTS: Carrying one DICER1 rs3742330*G allele conferred protection against developing ESRD [heterozygote comparison: OR = 0.30, 95% CI = 0.15‐0.62, dominant model: OR = 0.35, 95% CI = 0.17‐0.70]. Similarly, for XPO5 rs11077T/G, homozygote and heterozygote carriers of G variant were less likely to develop ESRD [homozygote comparison: adjusted OR = 0.23, 95% CI = 0.11‐0.50, and heterozygote comparison: OR = 0.50, 95% CI = 0.22‐0.92, and allelic model: OR = 0.46, 95% CI = 0.34‐0.70]. RAN rs14035*TT subjects were 5 times more likely to develop ESRD while being heterozygote (CT) have twice the risk [homozygote comparison: 5.18, 95% CI = 2.28‐11.8, heterozygote comparison: OR = 2.12, 95% CI = 1.10‐409]. Subgroup analysis also detected DICER1 rs3742330*A, XPO5 rs11077*T, and RAN rs14035*T as genetic risk determinants for ESRD development in both sex and age categories. Two genotype combinations of DROSHA/DICER1/XPO5/RAN were associated with increased susceptibility to ESRD [A‐A‐T‐T: OR = 9.49, 95%CI = 2.48‐36.31 (P = .001) and G‐A‐T‐T: OR = 5.92, 95%CI = 1.77‐19.83 (P = .004), respectively]. CONCLUSION: Variants and combined genotypes of DICER1 rs3742330, XPO5 rs11077, and RAN rs14035 might be associated with ESRD development in the study population. Integrating molecular analysis in ESRD risk stratification is warranted. John Wiley and Sons Inc. 2020-08-07 /pmc/articles/PMC7755820/ /pubmed/32770606 http://dx.doi.org/10.1002/jcla.23520 Text en © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Fawzy, Manal S.
Abu AlSel, Baraah T.
Toraih, Eman A.
Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end‐stage renal disease
title Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end‐stage renal disease
title_full Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end‐stage renal disease
title_fullStr Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end‐stage renal disease
title_full_unstemmed Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end‐stage renal disease
title_short Analysis of microRNA processing machinery gene (DROSHA, DICER1, RAN, and XPO5) variants association with end‐stage renal disease
title_sort analysis of microrna processing machinery gene (drosha, dicer1, ran, and xpo5) variants association with end‐stage renal disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755820/
https://www.ncbi.nlm.nih.gov/pubmed/32770606
http://dx.doi.org/10.1002/jcla.23520
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