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.
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.
Authors: David J Hunter; Marlies de Lange; Harold Snieder; Alex J MacGregor; R Swaminathan; Rajesh V Thakker; Tim D Spector Journal: Clin Sci (Lond) Date: 2002-09 Impact factor: 6.124
Authors: Frank Stam; Coen van Guldener; Casper G Schalkwijk; Piet M ter Wee; Ab J M Donker; Coen D A Stehouwer Journal: Nephrol Dial Transplant Date: 2003-05 Impact factor: 5.992
Authors: Caroline S Fox; Qiong Yang; L Adrienne Cupples; Chao-Yu Guo; Martin G Larson; Eric P Leip; Peter W F Wilson; Daniel Levy Journal: J Am Soc Nephrol Date: 2004-09 Impact factor: 10.121
Authors: Carl D Langefeld; Stephanie R Beck; Donald W Bowden; Stephen S Rich; Lynne E Wagenknecht; Barry I Freedman Journal: Am J Kidney Dis Date: 2004-05 Impact factor: 8.860
Authors: Michael G Shlipak; Linda F Fried; Casey Crump; Anthony J Bleyer; Teri A Manolio; Russell P Tracy; Curt D Furberg; Bruce M Psaty Journal: Circulation Date: 2003-01-07 Impact factor: 29.690
Authors: Patricia A Peyser; Lawrence F Bielak; Julia S Chu; Stephen T Turner; Darrell L Ellsworth; Eric Boerwinkle; Patrick F Sheedy Journal: Circulation Date: 2002-07-16 Impact factor: 29.690
Authors: Jenny van Dongen; Rick Jansen; Dirk Smit; Jouke-Jan Hottenga; Hamdi Mbarek; Gonneke Willemsen; Cornelis Kluft; Brenda W J Penninx; Manuel A Ferreira; Dorret I Boomsma; Eco J C de Geus Journal: Behav Genet Date: 2014-05-03 Impact factor: 2.805
Authors: Elizabeth G Holliday; Matthew Traylor; Rainer Malik; Stephen Bevan; Jane Maguire; Simon A Koblar; Jonathan Sturm; Graeme J Hankey; Christopher Oldmeadow; Mark McEvoy; Cathie Sudlow; Peter M Rothwell; Josef Coresh; Pavel Hamet; Johanne Tremblay; Stephen T Turner; Mariza de Andrade; Madhumathi Rao; Reinhold Schmidt; Peter A Crick; Antonietta Robino; Carmen A Peralta; J Wouter Jukema; Paul Mitchell; Sylvia E Rosas; Jie Jin Wang; Rodney J Scott; Martin Dichgans; Braxton D Mitchell; W H Linda Kao; Caroline S Fox; Christopher Levi; John Attia; Hugh S Markus Journal: Stroke Date: 2014-10-28 Impact factor: 7.914
Authors: J A Revez; L Bain; B Chapman; J E Powell; R Jansen; D L Duffy; J Y Tung; B W Penninx; P M Visscher; E J C De Geus; D I Boomsma; D A Hinds; N G Martin; G W Montgomery; M A R Ferreira Journal: Genes Immun Date: 2013-08-15 Impact factor: 2.676
Authors: György Jermendy; Tamás Horváth; Levente Littvay; Rita Steinbach; Adám L Jermendy; Adám D Tárnoki; Dávid L Tárnoki; Júlia Métneki; János Osztovits Journal: Cardiovasc Diabetol Date: 2011-11-03 Impact factor: 9.951
Authors: Marina Sirota; Gonneke Willemsen; Purnima Sundar; Steven J Pitts; Shobha Potluri; Edi Prifti; Sean Kennedy; S Dusko Ehrlich; Jacoline Neuteboom; Cornelis Kluft; Karen E Malone; David R Cox; Eco J C de Geus; Dorret I Boomsma Journal: PLoS One Date: 2015-04-08 Impact factor: 3.240