Heritability of renal function and inflammatory markers in adult male twins

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.

Fig. 1

a Univariate SEM with three latent factors on one measured phenotype. A = Additive genetic variance component; C = common environmental variance component; E = unique environmental variance component; a = genetic path coefficient; c = common environmental path coefficient; e = unique environmental path coefficient. Heritability h² = a²/(a² + c² + e²). b Bivariate Cholesky SEM decomposition. A1 = Genetic factor loading on both eGFR and inflammatory marker; A2 = genetic factor loading on inflammatory markers alone; E1 = unique environmental factor loading on both eGFR and inflammatory marker; E2 = unique environmental factor loading on inflammatory markers alone; a11–a22 = genetic path coefficients; e11–e22 = unique environmental path coefficients. a21 = 0 indicates that there is no genetic correlation between eGFR and inflammatory marker, and e21 = 0 indicates that there is no unique environmental correlation. For clarity only genetic (A) and unique environmental (E) factors are illustrated.