Cyrus Cyril, Chathoth Shahanas, Vatte Chittibabu, Alrubaish Nafie, Almuhanna Othman, Borgio J Francis, Al-Mueilo Samir, Al Muhanna Fahd, Al Ali Amein K
Department of Biochemistry, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Department of Internal Medicine, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Al-Khobar, Saudi Arabia.
Int J Nephrol. 2019 Aug 22;2019:1095215. doi: 10.1155/2019/1095215. eCollection 2019.
End-stage renal disease (ESRD) is the result of hypertensive nephrosclerosis and chronic glomerular diseases and is associated with high morbidity and mortality. There are strong heritable components in the manifestation of the disease with a genetic predisposition to renal disorders, including focal segmental glomerulosclerosis and arterionephrosclerosis. Recent studies in genetics have examined modifiable risk factors that contribute to renal disease, and this has provided a deep insight into progressive kidney disease. Single-nucleotide polymorphisms at the proximity of , CST3, , and genes have been associated with an increased risk of developing CKD and ESRD.
A total of 160 CKD patients and 189 control subjects of Saudi origin participated in the study. Eight polymorphisms (rs9992101, rs17319721; -rs4805834; -rs4821480, rs4821481, rs2032487, rs3752462; CST3-rs13038305) were genotyped using TaqMan assay, and the haplotype analysis was done using the HaploView 4.2 software.
Haplotype analysis revealed a ""-GTTT to be associated significantly with an increased risk for ESRD (=0.0001) and CKD (=0.03).
CKD is often silent until symptomatic uremia during the advanced stages of the disease. The newly identified haplotype will help recognize patients at risk for a rapid progression of CKD to ESRD. Accurate detection and mapping of the genetic variants facilitates improved risk stratification and development of improved and targeted therapeutic management for CKD.
终末期肾病（ESRD）是高血压性肾硬化和慢性肾小球疾病的结果，与高发病率和死亡率相关。该疾病的表现存在很强的遗传成分，具有肾脏疾病的遗传易感性，包括局灶节段性肾小球硬化和动脉硬化性肾病。遗传学方面的最新研究已经考察了导致肾脏疾病的可改变风险因素，这为深入了解进行性肾病提供了思路。位于CST3等基因附近的单核苷酸多态性与发生慢性肾脏病（CKD）和ESRD的风险增加有关。
共有160例沙特裔CKD患者和189例对照受试者参与了该研究。使用TaqMan分析对8个多态性位点（rs9992101、rs17319721；-rs4805834；-rs4821480、rs4821481、rs2032487、rs3752462；CST3-rs13038305）进行基因分型，并使用HaploView 4.2软件进行单倍型分析。
单倍型分析显示“-GTTT”与ESRD（P=0.0001）和CKD（P=0.03）风险增加显著相关。
CKD在疾病晚期出现有症状的尿毒症之前通常是隐匿的。新发现的单倍型将有助于识别有CKD快速进展至ESRD风险的患者。准确检测和定位基因变异有助于改善CKD的风险分层，并制定更好的针对性治疗管理方案。
