A Genome-Wide Association Study for Hypertensive Kidney Disease in Korean Men

Abstract

Hypertension is one of the major risk factors for chronic kidney disease (CKD), and the coexistence of hypertension and CKD increases morbidity and mortality. Although many genetic factors have been identified separately for hypertension and kidney disease, studies specifically focused on hypertensive kidney disease (HKD) have been rare. Therefore, this study aimed to identify loci or genes associated with HKD. A genome-wide association study (GWAS) was conducted using two Korean cohorts, the Health Examinee (HEXA) and Korean Association REsource (KARE). Consequently, 19 single nucleotide polymorphisms (SNPs) were found to be significantly associated with HKD in the discovery and replication phases (p < 5 × 10−8, p < 0.05, respectively). We further analyzed HKD-related traits such as the estimated glomerular filtration rate (eGFR), creatinine, blood urea nitrogen (BUN), systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the 14q21.2 locus, which showed a strong linkage disequilibrium (LD). Expression quantitative trait loci (eQTL) analysis was also performed to determine whether HKD-related SNPs affect gene expression changes in glomerular and arterial tissues. The results suggested that the FANCM gene may affect the development of HKD through an integrated analysis of eQTL and GWAS and was the most significantly associated candidate gene. Taken together, this study indicated that the FANCM gene is involved in the pathogenesis of HKD. Additionally, our results will be useful in prioritizing other genes for further experiments.

The genetic communication and interaction between chronic kidney diseases and frailty

“…conducted a large GWAS study of over 20 000 Korean men, and identified FANCM as the genetic gene associated with HKD. This research found that FANCM variation predominantly occurred in the glomerulus, tibial artery and aorta, and was strongly correlated with eGFR and creatinine ratio 45 …”

“…This research found that FANCM variation predominantly occurred in the glomerulus, tibial artery and aorta, and was strongly correlated with eGFR and creatinine ratio. 45 Despite the considerable strides made in genetic research on kidney function, there remains numerous difficulties in translating these findings into clinical practice for preventing or treating CKD and frailty. It is important to acknowledge that genetic diversity can vary based on race and ethnicity, which can impact the efficacy of drugs across different groups.…”

Evidence for a relationship between genetic polymorphisms of the L-DOPA transporter LAT2/4F2hc and risk of hypertension in the context of chronic kidney disease

“…Their coexistence has serious implications for human health increasing morbidity and mortality, especially from cardiovascular disease [22]. Several factors contribute to the concurrent presence of hypertension and kidney disease [23], including the contribution of a genetic component, as suggested by recent studies highlighting genes involved in both hypertension and kidney disease [24,25]. In the present study, to increase the understanding of the genetic connection in between, we evaluated the genetic variability of the heteromeric amino acid transporter LAT2/4F2hc (SLC7A8/SLC3A2 genes) in subjects strati ed according to presence/absence of CKD, evaluated by estimated glomerular ltration rate (eGFR), and presence/absence of hypertension.…”

Evidence for a relationship between genetic polymorphisms of the L-DOPA transporter LAT2/4F2hc and risk of hypertension in the context of chronic kidney disease

“…Their coexistence has serious implications for human health increasing morbidity and mortality, especially from cardiovascular disease [ 23 ]. Several factors contribute to the concurrent presence of hypertension and kidney disease [ 24 ], including the contribution of a genetic component, as suggested by recent studies highlighting genes involved in both hypertension and kidney disease [ 25 , 26 ]. In the present study, to increase the understanding of the genetic connection in between, we investigated the genetic variability of the SLC7A8/SLC3A2 genes, coding for the heteromeric transporter LAT2/4F2hc which mediates the cell-uptake of L-DOPA in kidney, in subjects stratified according to presence/absence of CKD and presence/absence of hypertension.…”