Alicja E Grzegorzewska1, Paulina Adamska2, Ewa Iwańczyk-Skalska3, Kamila Ostromecka4, Leszek Niepolski5, Wojciech Marcinkowski6, Adrianna Mostowska3, Wojciech Warchoł7, Czesław Żaba8, Paweł P Jagodziński3. 1. Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznań, Poland. alicja_grzegorzewska@yahoo.com. 2. Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznań, Poland. 3. Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 60-781, Poznań, Poland. 4. Nephrology Research Group, Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, 60-355, Poznań, Poland. 5. B. Braun Avitum Poland, Dialysis Center, 64-300, Nowy Tomyśl, Poland. 6. Fresenius Nephrocare Polska, 60-118, Poznań, Poland. 7. Department of Ophthalmology and Optometry, Poznan University of Medical Sciences, 60-806, Poznań, Poland. 8. Department of Forensic Medicine, Poznan University of Medical Sciences, 60-781, Poznań, Poland.
Abstract
Paraoxonase 1 (PON1) is known for preventing atherosclerosis through lipid-modifying features, antioxidant activity, anti-inflammatory, anti-apoptosis, anti-thrombosis, and anti-adhesion properties. Uremic patients requiring haemodialysis (HD) are especially prone to atherosclerosis and its complications. We analysed the PON1 gene (PON1) polymorphisms and serum PON1 (paraoxonase) activity concerning dyslipidaemia and related cardiovascular diseases and mortality to show how they associate under uremic conditions modified by maintenance HD treatment. The rs662 AA + AG (OR 1.76, 95%CI 1.10-2.80, P = 0.018), rs854560 TT (OR 1.48, 95%CI 1.04-2.11, P = 0.031), and rs854560 AT + TT (OR 1.28, 95%CI 1.01-1.63, P = 0.040) contributed to the prevalence of atherogenic dyslipidaemia diagnosed by the triglyceride (TG)/HDL-cholesterol ratio ≥ 3.8. The normalized serum PON1 activity positively correlated with atherogenic dyslipidaemia (ẞ 0.67 ± 0.25, P = 0.008). The PON1 rs854560 allele T was involved in the higher prevalence of ischemic cerebral stroke (OR 1.38, 1.02-1.85, P = 0.034). The PON1 rs705379 TT genotype contributed to cardiovascular (HR 1.27, 95% CI 1.03-1.57, P = 0.025) and cardiac (HR 1.34, 95% CI 1.05-1.71, P = 0.018) mortality. All P-values were obtained in multiple regression analyses, including clinical variables. Multifaceted associations of PON1 with dyslipidaemia, ischemic cerebral stroke, and cardiovascular mortality in HD patients provide arguments for the consideration of PON1 and its protein product as therapeutic targets in the prevention of atherosclerosis and its complications in uremic patients.
Paraoxonase 1 (n>an class="Gene">PON1) is known for preventing atherosclerosis through lipid-modifying features, antioxidant activity, anti-inflammatory, anti-apoptosis, anti-thrombosis, and anti-adhesion properties. Uremicpatients requiring haemodialysis (HD) are especially prone to atherosclerosis and its complications. We analysed the PON1 gene (PON1) polymorphisms and serum PON1 (paraoxonase) activity concerning dyslipidaemia and relatedcardiovascular diseases andmortality to show how they associate under uremic conditions modified by maintenance HD treatment. The rs662 AA + AG (OR 1.76, 95%CI 1.10-2.80, P = 0.018), rs854560 TT (OR 1.48, 95%CI 1.04-2.11, P = 0.031), and rs854560 AT + TT (OR 1.28, 95%CI 1.01-1.63, P = 0.040) contributed to the prevalence of atherogenic dyslipidaemiadiagnosed by the triglyceride (TG)/HDL-cholesterol ratio ≥ 3.8. The normalized serum PON1 activity positively correlated with atherogenic dyslipidaemia (ẞ 0.67 ± 0.25, P = 0.008). The PON1 rs854560 allele T was involved in the higher prevalence of ischemic cerebral stroke (OR 1.38, 1.02-1.85, P = 0.034). The PON1 rs705379 TT genotype contributed to cardiovascular (HR 1.27, 95% CI 1.03-1.57, P = 0.025) and cardiac (HR 1.34, 95% CI 1.05-1.71, P = 0.018) mortality. All P-values were obtained in multiple regression analyses, including clinical variables. Multifaceted associations of PON1 with dyslipidaemia, ischemic cerebral stroke, and cardiovascular mortality in HDpatients provide arguments for the consideration of PON1 and its protein product as therapeutic targets in the prevention of atherosclerosis and its complications in uremicpatients.
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