A Common <b><i>APOE</i></b> Polymorphism Is an Independent Risk Factor for Reduced Glomerular Filtration Rate in the Spanish RENASTUR Cohort

Abstract

Objective:APOE gene variants may contribute to the risk of chronic kidney disease. Our aim was to determine whether the common APOE-ε2/ε3/ε4 polymorphism is associated with a reduced estimated glomerular filtration rate (eGFR) in the RENASTUR population, a cohort of elderly individuals from the region Asturias (northern Spain). Methods: A total of 743 Spanish Caucasians aged 55-85 years were genotyped for the APOE-ε2/ε3/ε4 polymorphism. Individuals with a previous diagnosis of renal disease were not eligible for the study. Participants with a documented history of type 2 diabetes mellitus (T2DM) or hypertension or who were receiving antidiabetic or antihypertensive drugswere classified as diabetics and hypertensives. The eGFR was calculated using the Modification of Diet in Renal Disease formula, and those with an eGFR <60 ml/min/1.73 m² (n = 91) were considered as having impaired renal function. The effect of alleles and genotypes on clinical (hypertension, T2DM) and analytical findings was statistically determined. Results: In addition to age and T2DM, APOE-ε2 was significantly associated with an eGFR <60 ml/min/1.73 m² (p = 0.002; OR = 2.30). This association remained statistically significant after correction for multiple variables. Although the effect of the APOE-ε2 allele on the eGFR was observed both among diabetics and nondiabetics, the significance was stronger in the T2DM group. Conclusion: The APOE-ε2 allele is a genetic risk factor for impaired renal function among healthy elderly Spanish individuals.

Association betweenApolipoprotein EPolymorphism and Chronic Kidney Disease in the Korean General Population: Dong-gu Study

“… 14 , 17) However, other researchers have reported no association between APOE alleles and HDL cholesterol levels. 19 , 20) Many investigators have demonstrated that participants with the APOE E3 allele have the lowest triglyceride levels, 14 , 18 , 20) similar to our results. However, another study reported that female subjects with the APOE E2 allele have the lowest triglyceride levels.…”

“…Moreover, studies in general populations have not demonstrated consistent results. Some studies have reported a significant association between the APOE E2 allele and CKD, 19 , 20) whereas others indicate that the APOE E4 allele is associated with a decreased risk of CKD. 24 , 25) Yet others have reported no association between APOE polymorphisms and the prevalence of CKD.…”

“…Only APOE E2E3 and APOE E3E3 alleles were compared in the RENASTUR study with a Spanish Caucasian population. 20) Moreover, the definition of CKD 24 , 25) and the methods for estimating GFR 19 , 26) were different in each study.…”

Epigenetic considerations of the APOE gene

“…alzgene.org/). Besides AD and CVD, genetic studies have also connected APOE and its ε2/ε3/ε4 alleles to multiple physiological conditions and disorders, including aging (18,19), diabetes (20), dysbetalipoproteinemia (21), frontotemporal dementia (22), fragile X-associated ataxia (23), glomerulopathy (24), Lewy body dementia (25), metabolic syndrome (26), retinal-related disorders (27) disease (28), posttraumatic stress disorder (29), primary progressive aphasia (30), schizophrenia (31), stroke (32), traumatic brain injury (33), and vascular dementia (34).…”

Effect of the <b><i>FTO</i></b> rs9930506 Polymorphism on the Main Comorbidities of the Cardiorenal Metabolic Syndrome in an Elderly Spanish Cohort

“…They were recruited through the Primary Healthcare Center of the city of Oviedo to evaluate renal function in healthy elderly people, as reported [24]. Individuals with a history of renal disease or who had suffered episodes of cardiovascular disease were not eligible for the study.…”