title: Interaction between the Haptoglobin 2 Phenotype and Diabetes Mellitus on Systolic Pulmonary Arterial Pressure and Nitric Oxide Bioavailability in Hemodialysis Patients.
abstract: Elevated systolic pulmonary artery pressure (s-PAP, ≥35 mmHg) serves as an independent predictor of mortality in hemodialysis (HD) and diabetic (DM) patients. A polymorphism in the antioxidant Haptoglobin (Hp) gene has been shown to regulate the bioavailability of nitric oxide (NO), a major mediator of pulmonary vascular tone. We therefore set out to test the hypothesis that the Hp polymorphism may be a determinant of developing elevated s-PAP specifically in the DM state due to a decreased bioavailability of NO. To test our hypothesis we Hp typed and performed transthoracic echocardiography on a series of HD patients and stratified them into elevated and normal s-PAP groups and then evaluated whether there was a significant association between the Hp type, elevated s-PAP, and decreased NO bioavailability as defined by low plasma nitrite. We found a statistically significant interaction between the Hp type and DM on the prevalence of elevated s-PAP and lower mean nitrite levels with the combination of elevated s-PAP and low nitrite levels being significantly more prevalent in Hp 2-2 DM individuals. We conclude that the Hp 2 type is associated with elevated s-PAP levels and low plasma nitrite levels in HD patients specifically in the DM state.
authors.affiliation: Diabetic Nephropathy Laboratory, The Baruch Padeh Poriya Medical Center, Faculty of Medicine in the Galilee, 15208 The Lower Galilee, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Dahan
authors.affiliation: Division of Nephrology & Hypertension, The Baruch Padeh Poriya Medical Center, Faculty of Medicine in the Galilee, 15208 The Lower Galilee, Israel.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Farber
authors.affiliation: Diabetic Nephropathy Laboratory, The Baruch Padeh Poriya Medical Center, Faculty of Medicine in the Galilee, 15208 The Lower Galilee, Israel.
authors.forename: Nadia
authors.initials: N
authors.lastname: Thauho
authors.affiliation: Division of Nephrology & Hypertension, The Baruch Padeh Poriya Medical Center, Faculty of Medicine in the Galilee, 15208 The Lower Galilee, Israel.
authors.forename: Nakhoul
authors.initials: N
authors.lastname: Nakhoul
authors.affiliation: Division of Vascular Medicine, Holy Family Hospital, 16234 Nazareth, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Francis
authors.affiliation: Division of Vascular Medicine, Holy Family Hospital, 16234 Nazareth, Israel.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Awawde
authors.affiliation: Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 31096 Haifa, Israel.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Levy
authors.affiliation: Department of Physics and Translational Science Center, Wake Forest University, Reynolda Campus, Winston-Salem, NC 27109, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kim-Shapiro
authors.affiliation: Department of Physics and Translational Science Center, Wake Forest University, Reynolda Campus, Winston-Salem, NC 27109, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Basu
authors.affiliation: Diabetic Nephropathy Laboratory, The Baruch Padeh Poriya Medical Center, Faculty of Medicine in the Galilee, 15208 The Lower Galilee, Israel ; Division of Nephrology & Hypertension, The Baruch Padeh Poriya Medical Center, Faculty of Medicine in the Galilee, 15208 The Lower Galilee, Israel.
authors.forename: Farid
authors.initials: F
authors.lastname: Nakhoul
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D062186:Arterial Pressure; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism*; D004452:Echocardiography; D005260:Female; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011651:Pulmonary Artery / Q000000981:diagnostic imaging*; D011669:Pulmonary Wedge Pressure; D006435:Renal Dialysis
chemical_list: C485359:HP protein, human; D006242:Haptoglobins; D009573:Nitrites; D009569:Nitric Oxide