Heritability of Renal Function and Inflammatory Markers in Adult Male Twins

Overview

Journal Am J Nephrol

Publisher Karger

Specialty Nephrology

Date 2010 Aug 20

PMID 20720405

Citations 14

Authors

Paolo Raggi

Shaoyong Su

Cristina Karohl

Emir Veledar

Enrique Rojas-Campos

Viola Vaccarino

Affiliations

Soon will be listed here.

Abstract

Background: Loss of renal function is accompanied by a progressive increase in markers of inflammation; it is unknown whether they share common genetic pathways.

Study Design: We evaluated the shared heritability of estimated glomerular filtration rate (eGFR) and markers of inflammation and endothelial activation in 524 twin males from the Vietnam Era Twin Registry; 9 twins were excluded due to incomplete or incorrect data. Models were adjusted for age, race, body mass index, smoking, hypertension, diabetes mellitus, prior coronary artery disease and intercurrent medications.

Results: The mean eGFR was 89 ± 13 ml/min/1.73 m² (range 35-146); eGFR, intracellular adhesion molecule (ICAM) and TNF-α receptor (TNF-αR) were moderately heritable (all ∼50%), while IL-6 receptor (IL-6R) and P-selectin were highly heritable (68 and 76%, respectively). IL-6R and TNF-αR showed a significant inverse association with eGFR (p = 0.04 and p < 0.0001) while the association with ICAM and P-selectin was direct (p = 0.001 and p = 0.06). Bivariate structural equation models showed that the association between eGFR and biomarkers was due to unique environmental factors and there were no shared genetic pathways.

Conclusion: We found no shared genetic pathways between renal function and inflammation. Thus, increased inflammation represents a response to declining renal function rather than being a mechanism contributing to renal deterioration.

Citing Articles

Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.

Loeb G, Kathail P, Shuai R, Chung R, Grona R, Peddada S Nat Genet. 2024; 56(10):2078-2092.

PMID: 39256582 DOI: 10.1038/s41588-024-01904-6.

Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.

Loeb G, Kathail P, Shuai R, Chung R, Grona R, Peddada S bioRxiv. 2024; .

PMID: 38948875 PMC: 11212968. DOI: 10.1101/2024.06.18.599625.

Combing Genome-Wide Association Studies and Single-Cell Analysis to Elucidate the Mechanisms of Kidney Disease: Proceedings of the Henry Shavelle Professorship.

Levinsohn J, Li S, Ha E, Susztak K Glomerular Dis. 2023; 3(1):258-265.

PMID: 38033715 PMC: 10686632. DOI: 10.1159/000534678.

Polygenic association of glomerular filtration rate decline in world trade center responders.

Koraishy F, Mann F, Waszczuk M, Kuan P, Jonas K, Yang X BMC Nephrol. 2022; 23(1):347.

PMID: 36307804 PMC: 9615399. DOI: 10.1186/s12882-022-02967-5.

The Heritability of Kidney Function Using an Older Australian Twin Population.

Jefferis J, Pelecanos A, Catts V, Mallett A Kidney Int Rep. 2022; 7(8):1819-1830.

PMID: 35967118 PMC: 9366362. DOI: 10.1016/j.ekir.2022.05.012.

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