Iranian Journal of

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Background: Due to homeostatic and regulatory potentials of nitric oxide (NO) in vascular physiology, regulatory systems that determine NO bio-synthesis and bioavailability have been the subject of extensive research in molecular medicine. In the field of vascular system pathophysiology, endothelial nitric oxide synthase (eNOS) which is the major producer and regulator of NO in vascular tissues has received the most attention. Impairment of NO bioavailability (NO quenching) is a common feature in poorly controlled diabetics due to increased catabolism and decreased production of NO. Such impairment in severe forms could end to vasodilation breakdown in peripheral tissues (mainly in skeletal muscles) and defective regional blood flow, that in turn disturb insulin-dependent glucose uptake ensuing insulin resistance state.
Methods: The phenotypic impact of an eNOS gene polymorphism at position 786*C/T (that its functionality has been revealed already) on genetic propensity to diabetic retinopathy is evaluated in a British-Caucasian population with type 1 diabetes (T1DM).
Results: In contrast to genotypes, there was a significant difference in distribution of allele frequencies between T1DM patients (n= 249) and healthy controls (n= 104) (p= 0/036), that may imply eNOS and/or NO involvement in development of T1DM. Most notably a significant difference also was evident in allele frequency between retinopaths (n= 134) and healthy controls (p= 0/02). No significant difference was detected when the genotype/allele frequencies were compared between retinopaths (n= 134) and non-retinopaths diabetics (n= 115) (p=NS).
Conclusion: Our data is compatible with previous studies which demonstrated that allele C of eNOS 786*C/T polymorphism is associated with increased HbA1c levels. By emphasizing the phenotypic and prognostic value of the abovementioned polymorphism, our data calls for further investigations to find out whether this polymorphism can be employed as a genetic marker in clinical medicine to recognize high-risk diabetics at the time of diabetes onset/diagnosis.

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Background: Type 1 diabetes (T1DM) is an organ specific auto-immune disease, which is resulted by selective destruction of  islet cells. Insulitis as the initial event prior to T1DM development is featured mainly by lymphocytic infiltration, that may recede frequently leading to healthy state (benign insulitis). Among the issues that govern which of these outcome lie ahead in insulitis are the genetic background of the host and also the immunological circumstances in  islets' micro-environment.
Methods: As a "case-control association study" the impact of a polymorphism within TNF- gene at position -308*G/A on genetic susceptibility to T1DM is analyzed in a British-Caucasian population (248 cases and 118 healthy controls).
Results: The distribution of genotype/allele frequencies between patients and controls did not reflect significant differences (p= NS).
Conclusion: Since the crucial role of TNF- in development of T1DM is well established, our data may confer that the examined polymorphic marker does not have functional effects on TNF- gene expression, influencing the local or systemic level of this pro-inflammatory cytokine. However, in addition to addressing the uncertainties in "genotype-phenoype" correlations in complex diseases (i.e. T1DM), the negative results of our study also may instead draw attention to the potential impacts of post-transcriptional regulatory mechanisms relative to gene structural-based regulatory systems.

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Background: Despite substantial progress in the clinical management of diabetes, diabetic nephropathy (DN) still occurs recurrently, implicating diabetes as the major underlying condition leading to the end stage renal disease. One of the main reasons is the influential role of genetic or inherited backgrounds of diabetics that are almost overlooked in daily practice. Owing to be orchestrated by the genetic makeup, cellular and molecular responses are different to similar metabolic disturbances. This in turn defines susceptibility/resistance state of the host to chronic diabetic complications, including DN. Separate analysis of every single gene that may be involved in genetics of a multi-factorial disease (such as DN) is the only available way to dissect the genetic basis of the disease and overcome its complexity. Among different genes accountable for DN, Transforming Growth Factor (TGF)-1 has an exceptional place. TGF-1 has profound impact on cell growth and proliferation, and in particular the regulation of extra cellular matrix deposition, branding it as a "pro-fibrotic" and "hypertrophic" mediator.
Methods: By employing ARMS-PCR technique, the genetic susceptibility to DN was studied in 248 patients with T1DM (86 DN+, 162 DN−) and 113 healthy controls, all from British Caucasian origin. The analysis of two functional TGF-1 gene variations, which change codons 10 (+869*C/T) and 25 (+915*G/C) was carried out.
Results: There were some differences in alleles/genotypes distribution, but no significant association was apparent in patients as a whole or DN+/DN− subgroups and controls (P=NS). Conclusion: The negative result of this study may be false. As DN is a mortal disability, some fraction of risky genotypes associated with DN may previously be excluded by death. Such under-representation of the risky-genotypes (selective survivor effect) can be avoided by carrying out a prospective study. However, if the non-association result is true, it may question the functionality and reliability of the examined polymorphisms at least in the context of diabetes. Moreover, it does not underestimate the role of TGF-1 at the level of gene/protein themselves in development of DN.

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Background: Diabetes is the most common endocrine disorder that affects many people every year. Diabetic nephropathy is main complication of diabetes type 2. Renoprotective effects of vitamin “D” in chronic kidney disease have been reported that including diabetic nephropathy. The purpose of this study is to investigate the association between polymorphism (rs731236 (Taq1)) at gene receptor vitamin D (VDR), and the risk of diabetic nephropathy in patients with type 2 diabetes.
Methods In this case-control study, 104 patients with type 2 diabetes and nephropathy, 100 patients with type 2 diabetes and no nephropathy, and 98 people without diabetes and nephropathy who referred to the Diabetes Clinic of Tehran University of Medical Sciences were included .  Clinical data were obtained and biochemical parameters were measured. The DNA samples were extracted from blood samples by phenol chloroform method. TheTaqI polymorphism (rs731236) was studied by TaqMan specific genotypes.
Results: Urea, creatinine and urine albumin values were significantly higher and glomerular filtration rate was lower in nephropathy group. Although frequency of TT genotype and also T allele was higher in nephropathy group, the difference was not significant.
Conclusion: There was no association between Taq1 polymorphism and diabetic nephropathy in the studied population