Urinary Proteomics and Systems Biology Link Eight Proteins to the Higher Risk of Hypertension and Related Complications in Blacks Versus Whites DOI Creative Commons
De‐Wei An, Dries S. Martens, Gontse Mokwatsi

et al.

PROTEOMICS, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 24, 2024

ABSTRACT Blacks are more prone to salt‐sensitive hypertension than Whites. This cross‐sectional analysis of a multi‐ethnic cohort aimed search for proteins potentially involved in the susceptibility salt sensitivity, hypertension, and hypertension‐related complications. The study included individuals enrolled African Prospective Study on Early Detection Identification Cardiovascular Disease Hypertension (African‐PREDICT), Flemish Environment, Genes Health Outcomes (FLEMENGHO), Cohort Patients with Type 2 Diabetes Mellitus Validation Biomarkers (PROVALID)‐Austria, Urinary Proteomics Combined Home Blood Pressure Telemonitoring Care Reform Trial (UPRIGHT‐HTM). Sequenced urinary peptides detectable 70% participants allowed identification parental were compared between Of 513 peptides, 300 had significantly different levels among healthy Black ( n = 476) White 483) South Africans sharing same environment. Analyses contrasting 582 versus 1731 Whites, Sub‐Saharan European Whites replicated findings. COL4A1, COL4A2, FGA, PROC, MGP, MYOCD, FYXD2, UMOD identified as most likely candidates underlying racially related Enriched pathways hemostasis, platelet activity, collagens, biology extracellular matrix, protein digestion absorption. Our suggests that MGP MYOCD being cardiovascular function, FGA PROC coagulation, FYXD2 homeostasis, COL4A1 COL4A2 major components glomerular basement membrane many incriminated higher its complication. Nevertheless, these eight their associated deserve further exploration molecular human studies potential targets intervention reduce excess risk complications

Language: Английский

KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) DOI Creative Commons
Olivier Devuyst, Curie Ahn, Thijs R.M. Barten

et al.

Kidney International, Journal Year: 2025, Volume and Issue: 107(2), P. S1 - S239

Published: Jan. 21, 2025

Language: Английский

Citations

4
Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants DOI
Hongbo Liu, Amin Abedini, Eunji Ha

et al.

Science, Journal Year: 2025, Volume and Issue: 387(6734)

Published: Feb. 6, 2025

Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation newly signals on common variants European ancestry populations the power population diversity for further discoveries. We defined genotype effects allele-specific gene expression regulatory circuitries more than 700 human kidneys 237,000 cells. found 1363 coding disrupting 782 genes, with 601 genes also targeted by convergence 161 genes. Integrating 32 types information, present “Kidney Disease Genetic Scorecard” prioritizing potentially causal cell types, druggable targets kidney disease.

Language: Английский

Citations

2
Genetics of Chronic Kidney Disease DOI

Asaf Vivante

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(7), P. 627 - 639

Published: Aug. 14, 2024

The author discusses the diagnosis and management of CKD genetic origin in adults, focusing on single-gene variants that cause or confer a substantial risk progressive CKD.

Language: Английский

Citations

14
Alport syndrome and Alport kidney diseases – elucidating the disease spectrum DOI Creative Commons
Pongpratch Puapatanakul, Jeffrey H. Miner

Current Opinion in Nephrology & Hypertension, Journal Year: 2024, Volume and Issue: 33(3), P. 283 - 290

Published: March 13, 2024

Purpose of review With the latest classification, variants in three collagen IV genes, COL4A3 , COL4A4 and COL4A5 represent most prevalent genetic kidney disease humans, exhibiting diverse, complex, inconsistent clinical manifestations. This breaks down spectrum genotype–phenotype correlations diseases linked to these genes distinguishes “classic” Alport syndrome (AS) from less severe nonsyndromic genetically related nephropathies that we suggest be called “Alport diseases”. Recent findings Several research studies have focused on correlation under classification scheme AS. The historic diagnoses “benign familial hematuria” “thin basement membrane nephropathy” heterozygous or are suggested obsolete, but instead classified as autosomal AS by recent expert consensus due a significant risk progression. Summary concept extends beyond classic Patients carrying pathogenic any one COL4A3/A4/A5 can variable phenotypes ranging completely normal/clinically unrecognizable, hematuria without with proteinuria, progression chronic failure, depending sex, genotype, interplays other well environmental factors.

Language: Английский

Citations

12
Advancing Genetic Testing in Kidney Diseases: Report From a National Kidney Foundation Working Group DOI
Nora Franceschini, David L. Feldman, Jonathan S. Berg

et al.

American Journal of Kidney Diseases, Journal Year: 2024, Volume and Issue: 84(6), P. 751 - 766

Published: July 20, 2024

Language: Английский

Citations

10
Genome editing and kidney health DOI Creative Commons

Nadia Tavakolidakhrabadi,

Francesco Aulicino, Carl May

et al.

Clinical Kidney Journal, Journal Year: 2024, Volume and Issue: 17(5)

Published: April 17, 2024

ABSTRACT Genome editing technologies, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas in particular, have revolutionized the field of genetic engineering, providing promising avenues for treating various diseases. Chronic kidney disease (CKD), a significant health concern affecting millions individuals worldwide, can arise from either monogenic or polygenic mutations. With recent advancements genomic sequencing, valuable insights into disease-causing mutations be obtained, allowing development new treatments these disorders. CRISPR-based emerged as potential therapies, especially diseases, offering ability to correct and eliminate phenotypes. Innovations genome led enhanced efficiency, specificity ease use, surpassing earlier tools such zinc-finger nucleases transcription activator-like effector (TALENs). Two prominent gene are prime base editing. Prime allows precise efficient modifications without inducing double-stranded DNA breaks (DSBs), while enables targeted changes individual nucleotides both RNA DNA, correction absence DSBs. These technologies treat diseases through specific mutations, somatic PKD1 PKD2 polycystic disease; NPHS1, NPHS2 TRPC6 focal segmental glomerulosclerosis; COL4A3, COL4A4 COL4A5 Alport syndrome; SLC3A1 SLC7A9 cystinuria even VHL renal cell carcinoma. Apart sequence, CRISPR-mediated epigenome offers cost-effective method treatment therapeutic development, given that epigenetic associated with However, there challenges overcome, including developing delivery methods, improving safety reducing off-target effects. Efforts improve CRISPR-Cas involve optimizing vectors, employing viral non-viral approaches minimizing immunogenicity. research animal models results rescuing expression wild-type podocin mouse nephrotic syndrome successful clinical trials early stages disorders, cancer immunotherapy, is hope translation

Language: Английский

Citations

7
How Does ADPKD Severity Differ Between Family Members? DOI Creative Commons

Klement C. Yeung,

Elise Fryml,

Matthew B. Lanktree

et al.

Kidney International Reports, Journal Year: 2024, Volume and Issue: 9(5), P. 1198 - 1209

Published: Feb. 5, 2024

Thousands of pathogenic variants in more than 100 genes can cause kidney cysts with substantial variability phenotype and risk subsequent failure. Despite an established genotype-phenotype correlation cystic diseases, incomplete penetrance variable disease expressivity are present as is the case all monogenic diseases. In family members autosomal dominant polycystic (ADPKD), same causal variant responsible affected members; however, there still be striking discordance severity. This narrative review explores contributors to within-family ADPKD Cases biallelic digenic inheritance, where 2 rare cystogenic coexistent one family, account for a small proportion discordance. Genetic background, including cis trans factors polygenic propensity comorbid disease, also plays role but has not yet been exhaustively quantified. Environmental exposures, diet; smoking; alcohol, salt, protein intake, obesity, diabetes, hypertension, stones, dyslipidemia, additional diseases contribute phenotypic among members. Given that many contributing preventable, modifiable, or treatable, health care providers patients need aware these address them treatment ADPKD.

Language: Английский

Citations

6
Common Genetic Variants Modify Disease Risk and Clinical Presentation in Monogenic Diabetes DOI Creative Commons
James H. Leech, Robin N. Beaumont, Ankit M Arni

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Abstract The contribution of polygenic background in young onset monogenic disorders needs further exploration. Understanding this will provide new biological insights and may improve risk prediction disease. Here we investigated the role MODY—a common disorder with an age-dependent onset.We found strong enrichment type 2 diabetes (T2D) risk, but not 1 genetically confirmed MODY cases. This T2D burden, primarily through beta-cell dysfunction pathways, was strongly associated earlier age diagnosis increased severity. Common genetic variants collectively accounted for 24% (p<0.0001) phenotypic variability. Using a large population cohort, demonstrated that burden substantially modifies individuals pathogenic variants, ranging from 11% to 81%. Finally, show MODY-like phenotypes without causal variant had elevated related traits representing potential phenocopies. These findings reveal substantial influence variation shaping clinical presentation early-onset disorders. Incorporating these estimates carrying variants.

Language: Английский

Citations

0
Polygenic risk scores for eGFR are associated with age at kidney failure DOI Creative Commons
Kane E. Collins, Edmund Gilbert, Vincent Mauduit

et al.

Journal of Nephrology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Background The genetic architecture of chronic kidney disease (CKD) is complex, including monogenic and polygenic contributions. CKD progression to failure influenced by factors male sex, baseline estimated glomerular filtration rate (eGFR), hypertension, diabetes, proteinuria, the underlying disease. These traits all have strong components, which can be partially quantified using risk scores. This paper examines association between scores for CKD-related age at development. Methods Genome-wide genotype data from 10,586 patients with were compiled 12 cohorts. Polygenic albuminuria, rapid decline in eGFR, decreased total volume, eGFR calculated weights published independent population-scale genome-wide studies. each score was investigated logistic regression models. also separately primary Results Individuals highest 10% developed 2 years earlier than those bottom 90% (49.9 47.9 years, P = 5e-5). A standard deviation increase associated increased odds developing before 60 (Odds ratio (OR) 1.05; 95% CI 1.01–1.10; 0.01), as high (OR 1.26; 1.08–1.46; 0.003). Conclusions We conclude that explains a portion variation development failure. Graphical abstract

Language: Английский

Citations

0
Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A DOI
Shantanu Jain, Marena Trinidad, Thanh Nguyen

et al.

Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Language: Английский

Citations

0