Associations of genetic variants contributing to gut microbiota composition in diabetic nephropathy

IntroductionThe gut microbiota is strongly associated with multiple kidney diseases, and since microbial composition is heritable, we hypothesized that genetic variations controlling gut microbiota composition were associated with diabetic nephropathy susceptibility or clinical subphenotypes.Methods...

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Main Authors: Xiao Lu, Junjun Ma, Lili Guo, Wei Wu, Rongshan Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-12-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1264517/full
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author Xiao Lu
Junjun Ma
Lili Guo
Wei Wu
Rongshan Li
author_facet Xiao Lu
Junjun Ma
Lili Guo
Wei Wu
Rongshan Li
author_sort Xiao Lu
collection DOAJ
description IntroductionThe gut microbiota is strongly associated with multiple kidney diseases, and since microbial composition is heritable, we hypothesized that genetic variations controlling gut microbiota composition were associated with diabetic nephropathy susceptibility or clinical subphenotypes.MethodsThe genetic variations associated with gut microbiota were retrieved from the genome-wide association study database and analysed in our diabetic nephropathy susceptibility gene screening cohort. Candidate microorganisms with possible genetic associations were identified using the annotation of microbial quantitative trait loci. Finally, the candidate microorganisms were verified by 16S rDNA gene sequencing. ResultsThere were 13 genetic variation loci associated with susceptibility to diabetic nephropathy. The TCF7L2 risk genotype was associated with a long duration of diabetes and high diastolic blood pressure, the ZCWPW2 risk genotype was associated with increased glycosylated hemoglobin, and the ZNRF3 risk genotype was associated with an increased urinary microalbumin-to-creatinine ratio. Both the ZNRF3 and SPECC1L risk genotypes were associated with the abundance of Lactococcus. 16S rDNA sequencing confirmed that there was indeed a significant difference in the Lactococcus genus between DN and DM patients. ConclusionsIn this study, we preliminarily confirmed that the gut microbiota of diabetic nephropathy patients is influenced by host genetics and provide a new basis for future accurate diagnosis and treatment.
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spelling doaj.art-4ea920da74074ebeb1b06a9fff4773a02023-12-20T09:10:33ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-12-011410.3389/fendo.2023.12645171264517Associations of genetic variants contributing to gut microbiota composition in diabetic nephropathyXiao Lu0Junjun Ma1Lili Guo2Wei Wu3Rongshan Li4Department of Nephrology, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, ChinaDepartment of Thoracic Surgery, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, ChinaShanxi Provincial Key Laboratory of Kidney Disease, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, ChinaDepartment of Clinical Laboratory, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, ChinaDepartment of Clinical Laboratory, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People’s Hospital), Taiyuan, ChinaIntroductionThe gut microbiota is strongly associated with multiple kidney diseases, and since microbial composition is heritable, we hypothesized that genetic variations controlling gut microbiota composition were associated with diabetic nephropathy susceptibility or clinical subphenotypes.MethodsThe genetic variations associated with gut microbiota were retrieved from the genome-wide association study database and analysed in our diabetic nephropathy susceptibility gene screening cohort. Candidate microorganisms with possible genetic associations were identified using the annotation of microbial quantitative trait loci. Finally, the candidate microorganisms were verified by 16S rDNA gene sequencing. ResultsThere were 13 genetic variation loci associated with susceptibility to diabetic nephropathy. The TCF7L2 risk genotype was associated with a long duration of diabetes and high diastolic blood pressure, the ZCWPW2 risk genotype was associated with increased glycosylated hemoglobin, and the ZNRF3 risk genotype was associated with an increased urinary microalbumin-to-creatinine ratio. Both the ZNRF3 and SPECC1L risk genotypes were associated with the abundance of Lactococcus. 16S rDNA sequencing confirmed that there was indeed a significant difference in the Lactococcus genus between DN and DM patients. ConclusionsIn this study, we preliminarily confirmed that the gut microbiota of diabetic nephropathy patients is influenced by host genetics and provide a new basis for future accurate diagnosis and treatment.https://www.frontiersin.org/articles/10.3389/fendo.2023.1264517/fulldiabetic nephropathydiabetes mellitussusceptibility genesgut microbiotamicrobial quantitative trait locus
spellingShingle Xiao Lu
Junjun Ma
Lili Guo
Wei Wu
Rongshan Li
Associations of genetic variants contributing to gut microbiota composition in diabetic nephropathy
Frontiers in Endocrinology
diabetic nephropathy
diabetes mellitus
susceptibility genes
gut microbiota
microbial quantitative trait locus
title Associations of genetic variants contributing to gut microbiota composition in diabetic nephropathy
title_full Associations of genetic variants contributing to gut microbiota composition in diabetic nephropathy
title_fullStr Associations of genetic variants contributing to gut microbiota composition in diabetic nephropathy
title_full_unstemmed Associations of genetic variants contributing to gut microbiota composition in diabetic nephropathy
title_short Associations of genetic variants contributing to gut microbiota composition in diabetic nephropathy
title_sort associations of genetic variants contributing to gut microbiota composition in diabetic nephropathy
topic diabetic nephropathy
diabetes mellitus
susceptibility genes
gut microbiota
microbial quantitative trait locus
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1264517/full
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