SUN-218 Evaluation of common polymorphisms of eNOS gene and ACE gene in ADPKD patients and their association with HTN and renal failure in ADPKD patients

Abstract

Autosomal Dominant Polycystic kidney Disease (ADPKD) is the most common genetic cause of chronic kidney disease (CKD) and generally a late-onset multisystem disorder characterized by: bilateral renal cysts; cysts in multiple cysts in other organs. Renal manifestations include hypertension, renal pain, and renal insufficiency. Risk factors for progressive CKD include: younger age at the diagnosis, large kidney volume (size) on imaging, rapid cyst growth, hypertension, male gender, visible hematuria, and inheritance of a PKD1 versus a PKD2 mutation. The role of Angiotensin Converting Enzyme (ACE) gene polymorphism and endothelial nitric oxide synthase (eNOS) gene polymorphism in the clinical course of ADPKD is not well understood and there is no available index to predict the outcomes and clinical course of ADPKD. Our study evaluated association between these polymorphisms and presence of hypertension and renal failure in ADPKD patients. In this case-control study, 75 ADPKD patients and 100 control wasparticipated. All cases were provided written informed consent 5 cc of whole blood was obtained and transferred to the EDTA solutionand whole bloods was preserved in the temperature of -70◦ c◦ . then all samples of whole blood was referred to the genetic laboratory and DNA was extracted from whole blood by the phenol chloroform extraction and ethanol precipitation techniques. Genotyping for I/D polymorphism in ACE gene and Glu 298 ASP and T 786C polymorphisms in eNOS gene was performed by ARMS- PCR and molecular,s evaluation by special primers for two set genes ; I/D polymorphism in ACE gene and Glu 298 ASP and T 786C polymorphisms in eNOS gene was performed . There were no significant difference between two groups in terms of age and sex. The frequency of DD polymorphism of ACE gene and TC polymorphism of T786C of eNOS were significantly higher in ADPK patients than control but there was no difference in term of Glu 298ASP polymorphisms of eNOS gene. In ADPKD patients, 29 patients (39%) had hypertension, 4 patients (5%) had diabetes, 43 patients (57%) had GFR less than 60mL/min/1.73m2, and 41 patients (55%) had creatinine more than 1.5 mg/mL. The polymorphisms of ACE and eNOS genes were not significantly different in terms of hypertension, diabetes, GFR and creatinine status in ADPKD patients (P>0.05). There was no association between ACE polymorphisms and eNOS gene polymorphisms with renal insufficiency and hypertension in ADPKD patients. It seems that more number of patients need for study on association between polymorphisms and manifestation of ADPKD.