Heritability of renal function and inflammatory markers in adult male twins

Am J Nephrol. 2010;32(4):317-23. doi: 10.1159/000319449. Epub 2010 Aug 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Twin Study

MeSH terms

  • Biomarkers / blood*
  • Environment*
  • Glomerular Filtration Rate / genetics*
  • Humans
  • Inflammation / blood*
  • Inflammation / genetics*
  • Intercellular Adhesion Molecule-1 / blood
  • Intercellular Adhesion Molecule-1 / genetics
  • Kidney / metabolism
  • Kidney / physiology*
  • Male
  • Middle Aged
  • Models, Theoretical
  • P-Selectin / blood
  • P-Selectin / genetics
  • Receptors, Interleukin-6 / blood
  • Receptors, Interleukin-6 / genetics
  • Receptors, Tumor Necrosis Factor / blood
  • Receptors, Tumor Necrosis Factor / genetics
  • Twins

Substances

  • Biomarkers
  • P-Selectin
  • Receptors, Interleukin-6
  • Receptors, Tumor Necrosis Factor
  • Intercellular Adhesion Molecule-1