P1275PARAOXONASE 1 (PON1) GENE POLYMORPHISMS, PON1 EXPRESSION IN PBMCS, AND SERUM PON1 ACTIVITY CONCERNING DYSLIPIDEMIA AND RELATED COMORBIDITIES IN HEMODIALYSIS (HD) PATIENTS

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2020-06, Vol.35 (Supplement_3)
• Main Authors: Grzegorzewska, Alicja Ewa, Iwańczyk-Skalska, Ewa, Adamska, Paulina, Niepolski, Leszek, Mostowska, Adrianna, Warchoł, Wojciech, Jagodziński, Paweł
• Format: Article
• Language: English
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfaa142.P1275

Abstract Background and Aims PON1 may prevent atherosclerosis influencing lipid metabolism and exerting antioxidant and anti-inflammatory activities. We focused on serum PON1 activity in HD patients concerning dyslipidemia, coronary heart disease (CHD), myocardial infarction (MI), and cerebral stroke (CS). PON1 activity was related to PON1 polymorphisms, PON1 expression in PBMCs, and demographic, clinical, and laboratory data. Method In 93 HD patients (men 55, age 66.7, 18.3 – 86.2 years, renal replacement therapy duration 3.9, 0.2 – 22.3 years, CHD 25, MI 15, CS 9), dyslipidemia was diagnosed by K/DOQI guidelines. The TG/HDL-cholesterol ratio of ≥3.8 indicated atherogenic dyslipidemia. Standard diagnostic rules were applied for CHD, MI, and CS recognition. PON1 activity was measured in serum using an automated PON1 assay kit. PON1 polymorphisms were genotyped by high-resolution melting curve analysis (rs662) or using predesigned TaqMan SNV Genotyping Assay (rs854560 and rs705379). In 46 subjects, the relative PON1 transcript level was determined in PBMCs using reverse transcription-quantitative polymerase chain reaction analysis. Results In univariate analyses, the lower serum PON1 activity the higher frequency of mixed dyslipidemia (LDL ≥ 100 mg/dL, TG ≥ 200 mg/dL, non-HDL ≥ 130 mg/dl; β ± SE: -21.4 ± 10.0, P = 0.035) and the higher serum TG levels (β ± SE: -1.06 ± 0.49, P = 0.034). Normalized serum PON1 activity (the PON1/HDL ratio) correlated positively with male sex (β ± SE: 0.56 ± 0.25, P = 0.029), atherogenic dyslipidemia (β ± SE: 0.67 ± 0.25, P = 0.008), and cigarette smoking (β ± SE: 0.86 ± 0.42, P = 0.043). After adjustment for gender, cigarette smoking, urine output, living in rural area, and serum phosphorus, significance was maintained between normalized serum PON1 activity and atherogenic dyslipidemia (β ± SE: 0.54 ± 0.24, P = 0.028), male sex (β ± SE: 0.51 ± 0.24, P = 0.037) and cigarette smoking (β ± SE: 0.93±0.41, P = 0.024) as well as revealed for living in rural area (β ± SE: 0.55 ± 0.26, P = 0.039), urine output (β ± SE: -0.14 ± 0.07, P = 0.046), and zinc supplementation (β ± SE: 1.5 ± 0.67, P = 0.029). PON1 activity (101, 27.7 – 213 U/L) and normalized PON1 activity (2.27, 0.57 – 7.10) were not influenced by PON1 polymorphisms and did not yield differences in patients stratified by CHD, MI, CS, and dyslipidemic patterns except atherogenic dyslipidemia. The latter relationship was caused by a correlation between serum PON1 activity and