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Abstract: PO1105

Paraoxonase 1 Gene Polymorphisms Concerning Dyslipidemia, Related Comorbidities, and Mortality of Hemodialysis (HD) Patients

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Grzegorzewska, Alicja E., Poznan University of Medical Sciences, Poznan, Poland
  • Adamska, Paulina, Poznan University of Medical Sciences, Poznan, Poland
  • Ostromecka, Kamila, Poznan University of Medical Sciences, Poznan, Poland
  • Mostowska, Adrianna, Poznan University of Medical Sciences, Poznan, Poland
  • Warchol, Wojciech J., Poznan University of Medical Sciences, Poznan, Poland
  • Jagodzinski, Pawel P., Poznan University of Medical Sciences, Poznan, Poland
Background

Paraoxonase 1 (PON1), a protein product of PON1, may prevent atherosclerosis influencing lipid metabolism and exerting antioxidant and anti-inflammatory activities. We focused on PON1 polymorphisms concerning dyslipidemia, coronary heart disease (CHD), myocardial infarction (MI), ischemic cerebral stroke (ICS), and mortality of HD patients.

Methods

HD subjects (n = 1407, men 782, CHD 542, MI 299, ICS 250) were genotyped for PON1 polymorphisms by high-resolution melting curve analysis (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560 and rs705379). Dyslipidemia was diagnosed by K/DOQI guidelines (2003). The TG/HDL-cholesterol ratio of ≥3.8 indicated atherogenic dyslipidemia. Standard diagnostic rules were applied for CHD, MI, and ICS recognition. Survival probability was evaluated by the Kaplan-Meyer method and Cox regression analyses.

Results

The rs662 allele A (OR 1.70, 95% CI 1.07-2.70, P=0.023) and rs854560 TT vs. AA homozygosity (OR 1.59, 95% CI 1.09-2.32, P=0.017) contributed to the prevalence of atherogenic dyslipidemia. PON1 rs705379 was not associated with frequency of the TG/HDL-cholesterol ratios ≥3.8, but patients showing the TT genotype presented higher values of this ratio (3.92, 0.65–39.4) than possessors of the CC+CT genotypes (3.46, 0.44–49.7, P=0.039) or the CC genotype (3.42, 0.66–34.5, P=0.026). The T allele of PON1 rs854560 was associated with the higher prevalence of ICS (OR 1.38, 95% CI 1.02-1.85, P=0.034 together with age and diabetic nephropathy) and borderline with MI (OR 1.31, 95% CI 1.0-1.71, P=0.051 together with age, diabetic nephropathy, and male gender). The PON1 rs705379 TT genotype contributed to mortality from all cardiovascular diseases (HR 1.28, 95% CI 1.04-1.57, n=485, P=0.022), all cardiac diseases (HR 1.33, 95%CI 1.04-1.69, n=354, P=0.023), and CHD and its complications (HR 1.57, 95% CI 1.08-2.27, n=117, P=0.019).

Conclusion

All three tested PON1 polymorphisms correlate with atherogenic dyslipidemia in HD patients. Associations of PON1 with dyslipidemia, ICS, and cardiovascular mortality provide arguments for the consideration of PON1 as a therapeutic target in the prevention of atherosclerosis and its complications in uremic subjects.