Paraoxonase 1 gene variants concerning cardiovascular mortality in conventional cigarette smokers and non-smokers treated with hemodialysis.

Cigarette smoking effects might correspond with paraoxonase 1 gene (PON1) single nucleotide variants (SNVs). We investigated the association of PON1 rs705379, rs854560, and rs662 with cardiovascular mortality in hemodialysis (HD) patients concerning conventional cigarette smoking. Cardiovascular, cardiac, coronary heart disease (CHD)- and non-CHD-related deaths were analyzed in 206 HD cigarette smokers and 659 HD non-smokers. P-values were adjusted for sex, age, and high-density lipoprotein cholesterol. Among all smokers, the rs705379 TT genotype was associated with cardiovascular (P = 0.028), cardiac (P = 0.046), and cardiac non-CHD-related (P = 0.001) mortality. Non-diabetic smokers showed similar qualitative significance to all smokers concerning mentioned death rates (P-values 0.011, 0.044, and 0.009, respectively). In diabetic non-smokers, the rs705379 T allele correlated with CHD-related deaths (P = 0.020). The rs854560 T allele was associated with lower cardiovascular mortality in non-diabetic smokers (P = 0.008). The rs854560 TT genotype showed a negative non-significant correlation with non-CHD-related cardiac death in all non-smokers (P = 0.079). In diabetic smokers, the rs662 G allele was associated with higher cardiac mortality (P = 0.005). In all non-smokers and non-diabetic non-smokers, the rs662 G correlated with cardiovascular deaths (P = 0.020 and P = 0.018, respectively). Genotyping PON1 SNVs may help argue HD smokers harboring the rs705379 TT genotype or T allele and non-smokers possessing the rs662 G allele for prevention against cardiovascular diseases. These groups are more burdened genetically for cardiovascular mortality.

Paraoxonase 1 concerning dyslipidaemia, cardiovascular diseases, and mortality in haemodialysis patients.

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 gene polymorphisms concerning non-insulin-dependent diabetes mellitus nephropathy in hemodialysis patients.

AIMS: Data on involvement of paraoxonase 1 gene (PON1) in non-insulin-dependent diabetes mellitus (NIDDM) nephropathy are scarce. We investigated PON1 polymorphisms concerning end-stage NIDDM nephropathy and atherosclerotic complications in NIDDM nephropathy patients treated with hemodialysis (HD). METHODS: In NIDDM nephropathy (n = 402) and non-diabetic (n = 998) HD subjects, we obtained PON1 polymorphisms by HRM analysis (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). RESULTS: Only PON1 rs705379 was associated with end-stage NIDDM nephropathy in the recessive (OR 1.451, 95% CI 1.104-1.906, P = 0.009) and additive (OR 1.398, 95%CI 1.009-1.936, P = 0.046) inheritance modes. NIDDM nephropathy patients bearing the rs854560 T allele were at higher risk for ischemic cerebral stroke (OR 2.087, 95%CI 1.145-3.801, P = 0.016). In non-diabetic patients but not NIDDM nephropathy subjects, atherogenic dyslipidemia corresponded with PON1 rs662 A allele and PON1 rs854560 TT homozygosity. CONCLUSIONS: In HD patients, NIDDM nephropathy correlates with the TT genotype of PON1 rs705379. The rs854560 T allele indicates a higher risk for atherosclerotic diseases in NIDDM nephropathy subjects. The T alleles of both PON1 SNVs are known as low expression variants downregulated serum PON1 activity. An increase of diminished PON1 activity may be a target in the prevention of NIDDM nephropathy and NIDDM atherosclerotic complications.