Tumor Necrosis Factor Alpha 308 Genepolymorphism and Serum Osteoprotogerin Inarteriovenous Fistula Dysfunction Inhemodialysis Patients

Introduction The preservation of patent, well-functioning dialysis fistulas is one of the most difficult clinical problems in the long-term treatment of patients undergoing dialysis. Arteriovenous fistula (AVF) dysfunction remains a major contributor to the morbidity and mortality of hemodialysis patients. The goal is to identify a dysfunctional AVF early enough to intervene in a timely manner to either assist with the maturation process or to prevent thrombosis. Over the past years, numerous clinical studies have consistently reported higher serum levels of OPG in association with cardiovascular outcome including coronary artery disease (CAD), vascular calcification, advanced atherosclerosis. Genes encoding for TNF-alpha are potential genetic risk factors for atherosclerosis and have functional variants that regulate their expressions. Polymorphisms at the position ?308 in the promoter region of the TNF-alpha gene have been implicated as risk factors for atherosclerosis. Factor V Leiden mutation (G1691A) has been recognized to be the most prevalent genetic risk factor for venous thrombosis. Aim of the work The aim of the present work is to investigate TNF- alpha 308 gene polymorphism, factor V Leiden mutation (G1691A), and serum osteoprotogerin level in patients on maintenance hemodialysis suffering from vascular access dysfunction. Subjects & methods The study included 60 end stage renal disease patients from Alexandria University Hospitals on maintenance hemodialysis who were divided into 2 groups, 40 patients with AVF dysfunction, 20 patients with normal functioning AVF, 20 age and sex matched healthy subjects of matched age & sex were used as a control group. Investigations include serum level of Osteoprotogerin by ELISA technique, Serum TNF-alpha- 308Ggreater thanA-polymorphism by real time PCR and factor V Leiden gene mutation was assessed using 5' Nuclease assay as well as Doppler ultrasound for vascular access. Results As regard TNF alpha 308 gene polymorphism there was statistically significant difference in the group with dysfunctioning AVF compared to the other two groups while factor V laden gene mutation showed statistical significant difference in group with AVF dysfunction & control group while no significant difference between them and those with functioning AVF. OPG was higher in group with AVF dysfunction compared to those with functioning AVF & control group while there was no significant difference between functioning AVF & control group. Conclusion both OPG and the genotype distribution of TNF-? -308 G greater than A can be used as potential markers on HD patients to detect AVF dysfunction while, the role Factor V Leiden gene mutations may need further research and investigations. AVF dysfunction, TNF-alpha- 308Ggreater thanA-polymorphism, Osteoprotegrin ? factor V laden gene mutation.