المؤلفون: Marisa Cañadas-Garre, Blanca Baños-Jaime, Joaquín J. Maqueda, Laura J. Smyth, Ruaidhri Cappa, Ryan Skelly, Claire Hill, Eoin P. Brennan, Ross Doyle, Catherine Godson, Alexander P. Maxwell, Amy Jayne McKnight

المصدر: BMC Genomics, Vol 25, Iss 1, Pp 1-20 (2024)

مصطلحات موضوعية: Association, Chronic kidney disease, Diabetic kidney disease, Mitochondrial DNA, Mitochondrial haplogroups, Single nucleotide polymorphisms, Biotechnology, TP248.13-248.65, Genetics, QH426-470

الوصف: Abstract Background Chronic kidney disease (CKD) is a complex disorder that has become a high prevalence global health problem, with diabetes being its predominant pathophysiologic driver. Autosomal genetic variation only explains some of the predisposition to kidney disease. Variations in the mitochondrial genome (mtDNA) and nuclear-encoded mitochondrial genes (NEMG) are implicated in susceptibility to kidney disease and CKD progression, but they have not been thoroughly explored. Our aim was to investigate the association of variation in both mtDNA and NEMG with CKD (and related traits), with a particular focus on diabetes. Methods We used the UK Biobank (UKB) and UK-ROI, an independent collection of individuals with type 1 diabetes mellitus (T1DM) patients. Results Fourteen mitochondrial variants were associated with estimated glomerular filtration rate (eGFR) in UKB. Mitochondrial variants and haplogroups U, H and J were associated with eGFR and serum variables. Mitochondrial haplogroup H was associated with all the serum variables regardless of the presence of diabetes. Mitochondrial haplogroup X was associated with end-stage kidney disease (ESKD) in UKB. We confirmed the influence of several known NEMG on kidney disease and function and found novel associations for SLC39A13, CFL1, ACP2 or ATP5G1 with serum variables and kidney damage, and for SLC4A1, NUP210 and MYH14 with ESKD. The G allele of TBC1D32-rs113987180 was associated with higher risk of ESKD in patients with diabetes (OR:9.879; CI95%:4.440–21.980; P = 2.0E-08). In UK-ROI, AGXT2-rs71615838 and SURF1-rs183853102 were associated with diabetic nephropathies, and TFB1M-rs869120 with eGFR. Conclusions We identified novel variants both in mtDNA and NEMG which may explain some of the missing heritability for CKD and kidney phenotypes. We confirmed the role of MT-ND5 and mitochondrial haplogroup H on renal disease (serum variables), and identified the MT-ND5-rs41535848G variant, along with mitochondrial haplogroup X, associated with higher risk of ESKD. Despite most of the associations were independent of diabetes, we also showed potential roles for NEMG in T1DM.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2164Test

الوصول الحر: https://doaj.org/article/99d65bf485c945c2820dafe74e4345b0Test

المؤلفون: Marisa Cañadas-Garre, Andrew T. Kunzmann, Kerry Anderson, Eoin P. Brennan, Ross Doyle, Christopher C. Patterson, Catherine Godson, Alexander P. Maxwell, Amy Jayne McKnight

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 13, p 11209 (2023)

مصطلحات موضوعية: chronic kidney disease, diabetic kidney disease, genetic biomarkers, genetic risk score, UK Biobank, single nucleotide polymorphisms, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Increased albuminuria indicates underlying glomerular pathology and is associated with worse renal disease outcomes, especially in diabetic kidney disease. Many single nucleotide polymorphisms (SNPs), associated with albuminuria, could be potentially useful to construct polygenic risk scores (PRSs) for kidney disease. We investigated the diagnostic accuracy of SNPs, previously associated with albuminuria-related traits, on albuminuria and renal injury in the UK Biobank population, with a particular interest in diabetes. Multivariable logistic regression was used to evaluate the influence of 91 SNPs on urine albumin-to-creatinine ratio (UACR)-related traits and kidney damage (any pathology indicating renal injury), stratifying by diabetes. Weighted PRSs for microalbuminuria and UACR from previous studies were used to calculate the area under the receiver operating characteristic curve (AUROC). CUBN-rs1801239 and DDR1-rs116772905 were associated with all the UACR-derived phenotypes, in both the overall and non-diabetic cohorts, but not with kidney damage. Several SNPs demonstrated different effects in individuals with diabetes compared to those without. SNPs did not improve the AUROC over currently used clinical variables. Many SNPs are associated with UACR or renal injury, suggesting a role in kidney dysfunction, dependent on the presence of diabetes in some cases. However, individual SNPs or PRSs did not improve the diagnostic accuracy for albuminuria or renal injury compared to standard clinical variables.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/13/11209Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/9c9d3867893349169657a96a25039a43Test

المؤلفون: McKnight, Marisa Cañadas-Garre, Andrew T. Kunzmann, Kerry Anderson, Eoin P. Brennan, Ross Doyle, Christopher C. Patterson, Catherine Godson, Alexander P. Maxwell, Amy Jayne

المصدر: International Journal of Molecular Sciences; Volume 24; Issue 13; Pages: 11209

مصطلحات موضوعية: chronic kidney disease, diabetic kidney disease, genetic biomarkers, genetic risk score, UK Biobank, single nucleotide polymorphisms, cubilin

الوصف: Increased albuminuria indicates underlying glomerular pathology and is associated with worse renal disease outcomes, especially in diabetic kidney disease. Many single nucleotide polymorphisms (SNPs), associated with albuminuria, could be potentially useful to construct polygenic risk scores (PRSs) for kidney disease. We investigated the diagnostic accuracy of SNPs, previously associated with albuminuria-related traits, on albuminuria and renal injury in the UK Biobank population, with a particular interest in diabetes. Multivariable logistic regression was used to evaluate the influence of 91 SNPs on urine albumin-to-creatinine ratio (UACR)-related traits and kidney damage (any pathology indicating renal injury), stratifying by diabetes. Weighted PRSs for microalbuminuria and UACR from previous studies were used to calculate the area under the receiver operating characteristic curve (AUROC). CUBN-rs1801239 and DDR1-rs116772905 were associated with all the UACR-derived phenotypes, in both the overall and non-diabetic cohorts, but not with kidney damage. Several SNPs demonstrated different effects in individuals with diabetes compared to those without. SNPs did not improve the AUROC over currently used clinical variables. Many SNPs are associated with UACR or renal injury, suggesting a role in kidney dysfunction, dependent on the presence of diabetes in some cases. However, individual SNPs or PRSs did not improve the diagnostic accuracy for albuminuria or renal injury compared to standard clinical variables.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=multidiscipl::690a426f32251c41dde8555629860b70Test