Serum Paraoxonase Activity and Genotype Distribution in Japanese Patients with Diabetes Mellitus.

Sakai, Takenori; Matsuura, Bunzou; Onji, Morikazu

doi:10.2169/internalmedicine.37.581

Cited by 52 publications

(17 citation statements)

References 17 publications

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“…In contrast to most studies in Caucasians, all our subjects were Japanese undergoing coronary angiography to evaluate CAD without taking lipid-lowering drugs. In the analysis of the PON1 genotype in diabetic patients, one study demonstrated increased intima-media thickness (IMT) on carotid artery echogram in the Q/Q genotype (37), which is consistent with our results, but the other study showed no association between the IMT and PON1 genotypes (38). Another possibility related to factors affecting the antioxidant activity of PON1 is smoking.…”

Section: Discussionsupporting

confidence: 89%

R/R Genotype of Human Paraoxonase(PON1) is More Protective against Lipoprotein Oxidation and Coronary Artery Disease in Japanese Subjects.

Kuremoto

Watanabe

Ohmura

et al. 2003

JAT

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Human paraoxonase (PON1) is an high-density lipoprotein (HDL) -associated enzyme that is proposed to protect against the oxidation of lipoproteins. Recently, the association of coronary artery disease (CAD) and PON1 activity was reported. Furthermore, the R/R genotype of PON1 has been related to the risk for CAD. In this study we investigated the PON1 genotype and susceptibility to lipoprotein oxidation to elucidate the contribution of PON1 to atherosclerosis in Japanese subjects. We studied 179 patients who underwent coronary angiography and their PON1 genotypes were determined. Lipoproteins were obtained from a patient's blood after at least 12 hours fasting and were separated with sequential ultracentrifugation. We analyzed the thiobarbituric acid reactive substances (TBARS) and continuously monitored the copper-induced oxidation three genotype groups. Genotype frequencies of Q / Q, Q / R, and R / R were 21.2%, 36.9%, and 41.9%, respectively. PON1 polymorphism clearly determined the lipid oxidation. The R/R genotype of PON1 had significantly lower levels of plasma and HDL TBARS and significantly retarded the initiation of oxidation in HDL and low-density lipoprotein (LDL). The R/R genotype was related to the lower prevalence of CAD. The PON1 genotype clearly determined the oxidative modification of lipoproteins and may play a role in the pathogenesis of atherosclerosis via its protective effect against lipoprotein oxidation in Japanese subjects. J Atheroscler Thromb, 2003; 10: 85-92.

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Section: Discussionsupporting

confidence: 89%

R/R Genotype of Human Paraoxonase(PON1) is More Protective against Lipoprotein Oxidation and Coronary Artery Disease in Japanese Subjects.

Kuremoto

Watanabe

Ohmura

et al. 2003

JAT

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“…Both methylenetetrahydrofolate reductase (C677T) polymorphism causing Ala-toVal substitution and paraoxonase (Gln192Arg) polymorphism have been reported to show a positive association with carotid IMT (17,18). However, recent studies showed a negative result (19,20), so it remains unclear whether these genotypes can influence carotid IMT.…”

Section: Discussionmentioning

confidence: 99%

Antiatherogenic Mitochondrial Genotype in Patients With Type 2 Diabetes

Matsunaga

Tanaka

Tanaka³

et al. 2001

Diabetes Care

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OBJECTIVE -To evaluate the significance of a longevity-associated mitochondrial genotype (Mt5178A) derived from a C 3 A transversion at nucleotide position 5178 of mitochondrial DNA, which causes a Leu-to-Met substitution within the NADH dehydrogenase subunit 2 gene, in type 2 diabetic subjects.RESEARCH DESIGN AND METHODS -Mt5178 typing was done by polymerase chain reaction-restriction fragment-length polymorphism with the restriction enzyme AluI in 1,148 type 2 diabetic Japanese subjects, and the results were compared with the clinical characteristics. Then, the association of Mt5178 type with early atherosclerotic changes of the bilateral carotid arteries on ultrasonography was assessed in 412 diabetic subjects randomly selected from the original 1,148 type 2 diabetic subjects, while maintaining the same frequency of Mt5178A and Mt5178C.RESULTS -The frequency of Mt5178A in the type 2 diabetic subjects (454 of 1,148; 40%) was not different from that previously found in healthy blood donors (114 of 252; 45%). Clinical characteristics regarding diabetes were not significantly different between the Mt5178A group (n ϭ 454) and the Mt5178C group (n ϭ 694). However, the mean intima-media thickness (IMT) at six sites in the bilateral carotid arteries was significantly smaller in the Mt5178A group than in the Mt5178C group (0.906 Ϯ 0.018 vs. 0.995 Ϯ 0.021 mm, mean Ϯ SEM, P ϭ 0.022), and the Mt5178 type was significantly correlated with both the mean IMT and the presence of plaque on multiple regression analysis and discriminant analysis.CONCLUSIONS -The Mt5178A genotype may be unrelated to the etiology of type 2 diabetes. However, Mt5178A seems to have an antiatherogenic effect, at least in type 2 diabetic individuals. Diabetes Care 24:500 -503, 2001

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“…PON1 catalyzes the breakdown of organophosphates (Jakubowski, 2000;Josse et al, 2001) and also hydrolyzes homocysteine thio-lactone, which can harm some proteins by homocysteinylation. Reduced PON1 activities have been reported in cardiovascular diseases (McElveen et al, 1986;Navab et al, 1997), diabetes mellitus (Abbott et al, 1995;Mackness et al, 1998;Sakai et al, 1998), chronic renal failure (Dantoine et al, 1998), rheumatoid arthritis (Baskol et al, 2005), hyperthyroidism (Raiszadeh et al, 2004), age-related macular degeneration (Baskol et al, 2006) and in cataract (Hashim and Zarina, 2007).…”

Section: Introductionmentioning

confidence: 99%

Comparative efficacy of captopril and allylmercaptocaptopril in the maintenance of oxidative-antioxidative equilibrium and attenuation of selenite-induced cataract in rats

Lakshmi¹,

Sharma²

2011

International Journal of Biological and Chemical Sciences

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The present study was undertaken to investigate the comparative efficacy of captopril (CP) and allylmercaptocaptopril (AMC) supplementation following selenite exposure with respect to oxidant-antioxidant equilibrium and prevents cataract formation in rat pups. Forty Wistar-albino rat pups were equally divided into 4 groups. In Group I; only subcutaneous (s.c) saline was injected. In Group II; single dose of sodium selenite (19 µM/kg body weight, s.c) was injected on postpartum day 10. One day before the selenite challenge, the pups in Group III and IV were injected intraperitoneally a single dose of 50 mg/kg of CP and AMC respectively and repeated once daily thereafter up to 21 st day. The development of cataract was assessed weekly. The density of cataract was graded by slit-lamp biomicroscopy. On day 21, the blood was collected and lenses were removed. Total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI) and malondialdehyde (MDA) level were determined in the lenses of the rat pups. Serum paraoxonase-1 (PON1) activity was determined. All of the lenses of rat pups in Group I remained clean. All rat pups developed dense nuclear opacity in Group II. Three out of 10 rat pups developed slight nuclear opacity in Group III while only one rat pup out of 10 in Group IV had vacuolization but not opacity. Differences among the groups were statistically significant (p<0.01). Group II lenses had higher mean OSI and MDA level than those of Group III and IV (p<0.01). Group II lenses had lower mean TAC level and serum PON1 activity than those of Group III and IV (p<0.01). A negative correlation was found between serum PON1 activity and lens MDA level (r = -0.6861; P<0.001). CP and AMC both diminished the incidence of cataract due to its protection of the antioxidant defense system but AMC was found to be more effective than CP.

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Serum Paraoxonase Activity and Genotype Distribution in Japanese Patients with Diabetes Mellitus.

Cited by 52 publications

References 17 publications

R/R Genotype of Human Paraoxonase(PON1) is More Protective against Lipoprotein Oxidation and Coronary Artery Disease in Japanese Subjects.

R/R Genotype of Human Paraoxonase(PON1) is More Protective against Lipoprotein Oxidation and Coronary Artery Disease in Japanese Subjects.

Antiatherogenic Mitochondrial Genotype in Patients With Type 2 Diabetes

Comparative efficacy of captopril and allylmercaptocaptopril in the maintenance of oxidative-antioxidative equilibrium and attenuation of selenite-induced cataract in rats

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