Heritability of renal function and inflammatory markers in adult male twins.
BACKGROUND
Loss of renal function is accompanied by a progressive increase in markers of inflammation; it is unknown whether they share common genetic pathways.


METHODS
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.


CONCLUSIONS
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.
Raggi
Paolo
P
Department of Medicine, Emory University, Atlanta, GA, USA. praggi@emory.edu
Su
Shaoyong
S
Karohl
Cristina
C
Veledar
Emir
E
Rojas-Campos
Enrique
E
Vaccarino
Viola
V
D015415:Biomarkers / Q000097:blood*; D004777:Environment; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000235:genetics*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D019007:P-Selectin / Q000097:blood / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000097:blood / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000235:genetics; D014427:Twins
D015415:Biomarkers; D019007:P-Selectin; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D018799:Intercellular Adhesion Molecule-1