Genotype and Determinants of Urinary Uromodulin in African Populations

Overview

Journal Kidney Int Rep

Publisher Elsevier

Specialty Nephrology

Date 2024 Dec 19

PMID 39698369

Authors

Michel Strauss-Kruger

Eric Olinger

Patrick Hofmann

Ian J Wilson

Carina Mels

Ruan Kruger

Lebo F Gafane-Matemane

John A Sayer

Cristian Ricci

Aletta E Schutte

Olivier Devuyst

Affiliations

Soon will be listed here.

Abstract

Introduction: Single-nucleotide polymorphisms (SNPs) in the genetic locus are associated with chronic kidney disease (CKD) in European populations, through their effect on urinary uromodulin (uUMOD) levels. The genetic and nongenetic factors associated with uUMOD in African populations remain unknown.

Methods: Clinical parameters, 3 selected SNPs and uUMOD levels were obtained in 1202 young Black and White adults from the African-PREDICT study and 1943 middle aged Black adults from the PURE-NWP-SA study, 2 cross-sectional, observational studies.

Results: Absolute uUMOD and uUMOD/creatinine levels were lower in Black participants compared to White participants. The prime CKD-risk allele at rs12917707 was more prevalent in Black individuals, with strikingly more risk allele homozygotes compared to White individuals. Haplotype analysis of the locus predicted more recombination events and linkage disequilibrium (LD) fragmentation in Black individuals. Multivariate testing and sensitivity analysis showed that higher uUMOD/creatinine associated specifically with risk alleles at rs12917707 and rs12446492 in White participants and with higher serum renin and lower urine albumin-to-creatinine ratio in Black participants, with a significant interaction of ethnicity on the relationship between all 3 SNPs and uUMOD/creatinine. The multiple regression model explained a greater percentage of the variance of uUMOD/creatinine in White adults compared to Black adults (23% vs. 8%).

Conclusion: We evidenced ethnic differences in clinical and genetic determinants of uUMOD levels, in particular an interaction of ethnicity on the relationship between CKD-risk SNPs and uUMOD. These differences should be considered when analyzing the role of uromodulin in kidney function, interpreting genome-wide association studies (GWAS), and precision medicine recommendations.

Citing Articles

Ancestral Variability in the Genetic Architecture of Urine Uromodulin.

Lanktree M, Robinson-Cohen C Kidney Int Rep. 2025; 10(1):10-11.

PMID: 39810791 PMC: 11725962. DOI: 10.1016/j.ekir.2024.10.034.

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