Association of apolipoprotein E gene polymorphism with end-stage renal disease and hyperlipidemia in patients on long-term hemodialysis.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death of patients with chronic renal failure. Apolipoprotein E (apoE) plays an important role in the homeostasis of cholesterol and triglycerides. OBJECTIVE: We aimed to investigate the possible link(s) between apoE gene polymorphism, inflammation and lipoproteins in hemodialysis patients. METHODS: We studied 109 end-stage renal disease (ESRD) patients and 97 controls. The serum lipids, apolipoproteins, lipoprotein particles, high-sensitivity C-reactive protein (hs-CRP) and total homocysteine (t-Hcy) levels and paraoxonase (PON) activity were determined in our patients. We also analyzed apoE gene polymorphism in the patients and controls. RESULTS: The analysis of the apoE gene demonstrated a predominance of the e3 allele in both the patients and controls, followed by the e4 and then the e2 alleles. The analysis of the apoE genotype and allele frequencies showed significantly higher e4 allele and E3E4 genotype frequencies and decreased e3 allele and E3E3 genotype frequencies in the patients compared with the controls. The e2, e4 and E3E4 carriers within the ESRD patient population presented an atherogenic lipid profile. However, there were no significant variations in the serum PON activity and the hs-CRP and t-Hcy levels between individuals with different apoE polymorphisms. CONCLUSIONS: Our findings suggest an association between the e4 allele, E3E4 genotype and ESRD. The apoE polymorphism affects the serum lipoprotein levels, and the ESRD patients who are e4 and e2 allele carriers are more likely to present an atherogenic lipoprotein profile that may be a major factor associated with increased risk of CVD.

Serum paraoxonase activity, high-sensitivity C-reactive protein, and lipoprotein disturbances in end-stage renal disease patients on long-term hemodialysis.

BACKGROUND: Hemodialysis patients are at high risk for atherosclerotic events. Enhanced oxidant stress, dyslipidemia, and inflammation may have a major role in this risk. In this work, we assessed lipoprotein status, total homocysteine, high-sensitivity C-reactive protein (hs-CRP), and paraoxonase activity in hemodialysis patients to determine the correlations among these parameters and to compare these values with those measured in normal control subjects. METHODS: We enrolled 109 end-stage renal disease patients on long-term hemodialysis and 100 age- and gender-matched healthy subjects. Total cholesterol, triglycerides, and high-density lipoprotein cholesterol levels were evaluated using colorimetric methods. Low-density lipoprotein (LDL) cholesterol was calculated according to the Friedewald formula. Serum levels of hs-CRP, apolipoproteins (Apo) AI, B, E, and lipoprotein(a) were measured by nephelometry. Lipoprotein particle (Lp) A-I and LpA-I:A-II were determined by immunoelectrophoresis. Total homocysteine levels were evaluated by the fluorescence polarization immunoassay method. Paraoxonase activity was determined using the paraoxon-like substrate. RESULTS: Compared with controls, hemodialysis patients had more frequent atherogenic dyslipidemia, hyperhomocysteinemia, and elevated hs-CRP levels. These latter findings inversely correlate with ApoA-I and LpA-I:A-II and positively with ApoB, lipoprotein(a), and ApoB/ApoA-I ratio. Homocysteine levels correlated positively with age. Paraoxonase activity was decreased in hemodialysis patients, especially in elderly patients. This enzyme activity positively correlated with LpA-I:A-II, and inversely with hs-CRP, LDL-cholesterol, and ApoE levels. CONCLUSION: The present study demonstrated an abnormal lipoprotein profile associated with increased hs-CRP and decreased paraoxonase activity in hemodialysis patients. Hence, inflammation, dyslipidemia, and increased oxidant stress linked to uremia may be contributors to increased cardiovascular risk in this population.