Source

Ankara University, Faculty of Pharmacy, Department of Toxicology, 06100, Tandogan, Ankara, Turkey.

Abstract

OBJECTIVES:

We investigated whether the human serum paraoxonase (PON1) Q/R 192 and M/L 55 polymorphisms are associated with the complications of the type 2 diabetes (T2D).

DESIGN AND METHODS:

Study group was consisted of 50 healthy subjects and 100 type 2 diabetes mellitus (DM) patients. Following measuring of serum PON1 activity, isolation of DNA and genotyping analyses were performed.

RESULTS:

PON1 activity of the patients with complications was significantly reduced by 23.5% compared to the group of diabetic patients and by 26.3% than the controls. According to multivariate analysis, we observed a three times significant effect of Q/R 192 polymorphism on the susceptibility to the occurrence of complications.

CONCLUSIONS:

Protective effects of paraoxonase against peroxidation of LDL particles are important in T2D complications. Although both of the two polymorphisms are associated, 192 polymorphism seems to be stronger predictor of the risk of diabetic complications.

Abstract

OBJECTIVES: We investigated whether the human serum paraoxonase (PON1) Q/R 192 and M/L 55 polymorphisms are associated with the complications of the type 2 diabetes (T2D).

DESIGN AND METHODS: Study group was consisted of 50 healthy subjects and 100 type 2 diabetes mellitus (DM) patients. Following measuring of serum PON1 activity, isolation of DNA and genotyping analyses were performed.

RESULTS: PON1 activity of the patients with complications was significantly reduced by 23.5% compared to the group of diabetic patients and by 26.3% than the controls. According to multivariate analysis, we observed a three times significant effect of Q/R 192 polymorphism on the susceptibility to the occurrence of complications.

CONCLUSIONS: Protective effects of paraoxonase against peroxidation of LDL particles are important in T2D complications. Although both of the two polymorphisms are associated, 192 polymorphism seems to be stronger predictor of the risk of diabetic complications.

Abstract

The most well-known metabolic pathways from ethanol to acetaldehyde include alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system that involves cytochrome P450 2E1 (CYP2E1). Acetaldehyde is further oxidized to acetate by aldehyde dehydrogenase (ALDH). The genetic variation of ADH1B, ALDH2, and CYP2E1 is different among racial populations and cause difference in elimination rates of alcohol. The aim of this study was to determine the polymorphisms of ADH1B (rs1229984; Arg47His), ALDH2 (rs671; Glu487Lys), CYP2E1*6 (rs6413432; T7632A), and CYP2E1*7B (rs6413420; G-71T) in unrelated healthy Turkish population and compare it with other populations. ADH1B and ALDH2 polymorphisms were analyzed with an allele-specific polymerase chain reaction (PCR) assay, and CYP2E1*6 and CYP2E1*7B polymorphisms were genotyped by PCR-restriction fragment length polymorphism method. ADH1B polymorphism analysis yielded the genotype distribution as 83.9% ADH1B*1/1 and 16.1% ADH1B*1/2, and no individuals with ALDH2*1/2 and ALDH2*2/2 genotypes were found in Turkish population. The genotype frequencies for CYP2E1*6 polymorphism were found as 85.3% for homozygote common, 14.1% for heterozygote, and 0.6% for homozygote uncommon. For CYP2E1*7B polymorphism, the genotype frequencies were determined to be 86.5% G/G, 13.5% for G/T; however, no individuals with homozygote uncommon genotype were detected. According to our study results, the genotype distributions of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B in Turkish population were similar compared with Caucasian and some European populations, whereas differed significantly from East Asian populations. This study may be useful in epidemiological studies of the influence of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B polymorphisms on diseases, including several types of cancer related to alcohol consumption and alcohol dependence. Copyright © 2010 Elsevier Inc. All rights reserved.

Abstract

Context: There are controversial results and insufficient knowledge in the literature about the genetics of diabetes mellitus complications in the Turkish population and endothelial nitric oxide synthase (eNOS) gene polymorphisms may act as a potential modifier of diabetic vascular complications. Objective: The objective of this study was to determine the association between eNOS G894T polymorphisms and diabetes-related diseases. Design: A Turkish case-control study was designed. Setting: The study was carried out in the Ankara University Hospital. Patients or Other Participants: Totally, 97 Turkish patients with diabetic foot ulcers and 102 controls were enrolled. Patients who had not received antimicrobial treatment in the preceding 6 months were included. Diabetic patients with hand and/or foot ulcers resulting from major trauma, such as road traffic accidents, were excluded. Main Outcome Measure: The effect of eNOS gene polymorphisms on diabetic complications and comorbid diseases was measured. Results: Regarding eNOS G894T gene polymorphisms, 47.4% of the patients had GG (n = 46), 47.4% (n = 46) had GT, and 5.2% (n = 5) had TT alleles in the diabetes mellitus group, and 47.0% (n = 48), 41.2% (n = 42), and 11.8% (n = 12) had GG, GT, and TT alleles in the control group, respectively. There was no significant difference between the groups regarding the eNOS G894T gene allele ratios. Between groups with and without diabetic complications, a significant difference has only been found in the distribution of alleles in patients with comorbid atherosclerotic heart disease, whose GT-TT alleles were significantly higher than the GG alleles (p = 0.004). Conclusion: G894T polymorphism of eNOS gene was not associated with foot ulcer and diabetic complications, except in the presence of atherosclerotic heart disease.