Abstract 033: Genetic Polymorphisms Associated With Apparent Treatment-Resistant Hypertension in Patients With Chronic Kidney Disease

Abstract

The risk of suffering from apparent treatment-resistant hypertension (ATRH) increases more than 4-folds in patients with chronic kidney disease (CKD) comparing to general population, although causes unknown. We hypothesize that genetic variants of certain inflammatory factors occur in CKD patients with ATRH, which may serve as distinct genetic signature for ATRH. Data from Chronic Renal Insufficiency Cohort (CRIC) study were used to identify genetic variants related to ATRH among CKD patients. ATRH was defined as mean SBP/DBP ≥140/90 mm Hg while taking ≥3 antihypertensive medications or <140/90 mm Hg while taking ≥4 antihypertensive medications at the baseline visit. Clean genotype data on chromosome 6 from genotyped or imputed single-nucleotide polymorphisms (SNPs) were available for 3,263 patients (1,172 with ATRH and 2,091 without ATRH) in CRIC. Logistic regressions were carried out comparing distribution of SNPs among CKD patients with or without ATRH, controlling for confounding factors. Among 63,517 SNPs on chromosome 6, we found SNPs on three genes that were putative risk genes for ATRH among CKD patients (P-value<5х10 -4 ). PHACTR1 (rs6900427) encodes for phosphatase and actin regulator 1, which plays a role in endothelial cell survival, and its variants have been associated with myocardial infarction and coronary artery disease. PPARD (rs6915115) encodes for peroxisome proliferator activated receptor delta, which has been implicated as an important inflammatory regulator including a role in the NF-κB pathway. Finally, PRKN (rs10945756) encodes for parkin RBR E3 ubiquitin protein ligase, which plays a role in mediating degradation of proteins including tumor necrosis factor receptor-associated factor 3 (TRAF3) that has been suggested to participate in the control of inflammation. Thus, these results are the first demonstrating that distinct genetic polymorphisms present in CKD patients with ATRH, which may serve as unique genetic signature for predisposed risk of ATRH. Moreover, association between predisposition of inflammatory factors and ATRH may implicate a role of inflammation in ATRH pathogenesis, revealing potential therapeutic targets.