Alicja E Grzegorzewska1, Kamila Ostromecka2, Paulina Adamska2, Adrianna Mostowska3, Wojciech Warchoł4, Paweł P Jagodziński5. 1. Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, Przybyszewskiego 49, Poland. Electronic address: agrzegorzewska@ump.edu.pl. 2. Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznań, Przybyszewskiego 49, Poland. 3. Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 60-781 Poznań, Święcickiego 6, Poland. 4. B. Braun Avitum Poland, Dialysis Center, 64-300 Nowy Tomyśl, Sienkiewicza 3, Poland; Department of Ophthalmology and Optometry, Poznan University of Medical Sciences, Poznań, Poland. Electronic address: wwarchol@ump.edu.pl. 5. Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 60-781 Poznań, Święcickiego 6, Poland. Electronic address: pjagodzi@ump.edu.pl.
Abstract
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.
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 nephropathypatients 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 PON1rs705379 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 nephropathypatients 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-diabeticpatients but not NIDDM nephropathy subjects, atherogenic dyslipidemia corresponded with PON1rs662 A allele and PON1rs854560 TT homozygosity. CONCLUSIONS: In HDpatients, NIDDM nephropathy correlates with the TT genotype of PON1rs705379. 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.
Authors: Alicja E Grzegorzewska; Adrianna Mostowska; Wojciech Warchoł; Paweł P Jagodziński Journal: BMC Infect Dis Date: 2021-08-26 Impact factor: 3.090