title: Obesity-associated hypertension is ameliorated in patients with TLR4 single nucleotide polymorphism (SNP) rs4986790.
abstract: BACKGROUND
  Obesity is strongly associated with hypertension. Despite numerous mechanistic links the association is not fully understood. Western diet increases uptake of Toll-Like receptor 4 (TLR4) ligands such as free fatty acids or endotoxin. We recently demonstrated that TLR4 ligands are involved in the development of hypertension. We hypothesized that TLR4 ligands are involved in obesity-associated hypertension and investigated the TLR4 single nucleotide polymorphism (SNP rs 498790). This SNP is frequent, associated with cardiovascular disease and characterized by blunted response upon exposure to TLR4 ligands.
  
  
  METHODS
  We investigated 3657 patients undergoing coronary angiography. Blood pressure was determined in standardized manner prior angiography. The diagnosis of hypertension was based on record data. Patients were characterized for TLR4 single nucleotide polymorphism (SNP) rs4986790. Patients were stratified according to quartiles of Body mass index (BMI) and according to the polymorphism. The association between the TLR4 polymorphism and blood pressure in obese patients (BMI > 30 kg/m(2)) was investigated by multivariate regression analysis.
  
  
  RESULTS
  Out of 3657 patients 3017 patients fulfilled inclusion criteria. In the whole cohort a significant increase of SBP, pulse pressure and diagnosis of hypertension was observed across BMI quartiles. By contrast, no significant increase of SBP, pulse pressure or diagnosis of hypertension was observed in the 319 cases with TLR4 SNP rs4986790 across BMI quartiles. These obese cases had significantly lower SBP, lower pulse pressure (7.0 and 7.6 mmHg) and less diagnosis of hypertension as controls. In obesity the TLR4 SNP rs4986790 was an independent predictor of SBP.
  
  
  CONCLUSIONS
  Systolic blood pressure increase with obesity was blunted in cases with TLR4 SNP rs4986790.
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schneider
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Hoppmann
authors.affiliation: Deutsches Herzzentrum München, Technical University Munich, Munich, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Koch
authors.affiliation: Department of Nephrology, Klinikum rechts der Isar, Technical University Munich, Ismaninger St. 22, 81675 Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kemmner
authors.affiliation: Department of Nephrology, Klinikum rechts der Isar, Technical University Munich, Ismaninger St. 22, 81675 Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmaderer
authors.affiliation: Department of Nephrology, Klinikum rechts der Isar, Technical University Munich, Ismaninger St. 22, 81675 Munich, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Renders
authors.affiliation: Deutsches Herzzentrum München, Technical University Munich, Munich, Germany.|German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
authors.affiliation: I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.|German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Laugwitz
authors.affiliation: Department of Nephrology, Klinikum rechts der Isar, Technical University Munich, Ismaninger St. 22, 81675 Munich, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Heemann
authors.affiliation: Department of Nephrology, Klinikum rechts der Isar, Technical University Munich, Ismaninger St. 22, 81675 Munich, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Baumann
keywords: Genetics; Obesity associated hypertension; Systolic blood pressure; TLR4; Toll-like receptor 4