Apolipoprotein E gene polymorphism and renal function are associated with apolipoprotein E concentration in patients with chronic kidney disease

Abstract

Background: Chronic kidney disease (CKD) associates with complex lipoprotein disturbances resulting in high cardiovascular risk. Apolipoprotein E (APOE) is a polymorphic protein with three common isoforms (E2; E3; E4) that plays a crucial role in lipoprotein metabolism, including hepatic clearance of chylomicrons and very low-density lipoprotein (VLDL) remnants, and reverse cholesterol transport. It demonstrates anti-atherogenic properties but data concerning the link between polymorphism and level of APOE in CKD patients are inconclusive. The aim of our research was to assess the relationship between APOE gene polymorphism and APOE concentration and its redistribution among lipoproteins along with CKD progression. Methods: 90 non-dialysed CKD patients were included into the study. Real time PCR was used for APOE genotyping. APOE level was measured in serum and in isolated lipoprotein fractions (VLDL; IDL + HDL; HDL). Kidney function was assessed using eGFR CKD-EPI formula. Results: The population was divided into three APOE genotype subgroups: E2(ε2ε3), E3(ε3ε3) and E4(ε3ε4). The highest APOE level was observed for the E2 subgroup (p < 0.001). APOE concentration positively correlated with eGFR value in the E2 subgroup (r = 0.7, p < 0.001) but inversely in the E3 subgroup (r = − 0.29, p = 0.02).). A lower concentration of APOE in the E2 subgroup was associated with its diminished contents in HDL and IDL + LDL particles. In the E3 subgroup, the higher concentration of APOE was related to the increased number of non-HDL lipoproteins. Conclusion: In patients with CKD, APOE genotype as well as renal function are associated with the concentration of APOE and its redistribution among lipoprotein classes.

Association between apolipoprotein E polymorphism and lipid profile in patients of myocardial infarction

“…Alterations of lipid profile could be associated with acceleration of atherosclerosis and higher risk of incident CVD. 30 Moreover, obesity, smoking, etc. conditions associated with high oxidative stress, can aggravate the progression of disease and genetic studies can thus provide information that may help to improve the ability to identify individuals, families and populations at increased risk, and to improve the clinical management of patients of MI.…”

Apolipoprotein E Gene Polymorphism and Coronary Artery Disease Risk Among Patients in Northwest China

“…The precise cellular mechanisms which are responsible for the differences between ε2, ε3 and ε4 are not fully understood, but ε4 has a somewhat higher affinity for the LDL receptor than ε3, while ε2 bind less well to the receptor-only 2% of normal activity, which results in different plasma lipoprotein profiles. 19 ε4 is associated with elevated levels of TC, LDL-C, TG and ApoB, lower plasma levels of ApoE, and an increased CAD incidence. 20 , 21 A large meta-analysis demonstrated that ε2 carriers have a 20% lower CAD risk compared with ε3 or ε4 carriers.…”

“… 35 We also observed that ɛ4 carriers had a significantly lower ApoE in both groups, which was consistent with previous findings of the ApoE level being highest in ɛ2 carriers and lowest in ɛ4 carriers. 19 , 36 …”

Age modulates protein-outcome associations in deceased donor kidneys

“…Another age-moderated protein, APOE stands out as having previously reported agerelated associations with disease and organ dysfunction, in both cases including Alzheimer's Disease (AD). APOE plays an important role in lipid metabolism to regulate the growth and survival of mesangial cells and preserve kidney function 49 ; not only is APOE protein a marker for outcome in transplant recipients [50][51][52] , there is also evidence for particular APOE genetic alleles being associated with dysfunction risk [53][54][55] , possibly manifested directly by lipidomic differences between allelic profiles 56 . APOE alleles are further implicated in a host of disorders including age-moderated association with AD risk 57 (with the strongest effect manifesting around age 65 58 ), macular dysfunction, atherosclerosis and pulmonary scarring 59,60 .…”