Showing 23 results for Polymorphism
Mehdi Zamani, Jean Neijrup, Janjes Kasmian,
Volume 1, Issue 1 (7-2001)
Abstract
Background: Numerous studies have confirmed the association between type 1 diabetes mellitus (DM1) and polymorphisms of HLA genes on chromosome 6p21. Controlled DNA studies in Belgium recently have found a statistically significant association between DM1 and certain HLA class II genes, especially DRB1Lys71+.
Methods: 81 Danish families (each with at least 2 members with DM1) and 82 healthy controls were assessed for HLA polymorphisms. 54 of the 81 diabetic families were also assessed for polymorphisms at the HLA-B-DQB1, HLA-B-DQA1, and TNF-A and TNF-B loci. Affected sib-pair analysis was used to study correlation between DM1 and DRB1 alleles encoding Lys71+.
Results: Homozygous expression of DRB1Lys71+ carried a relative risk (RR) of 103.5 for DM1. There was a very strong correlation (p<1×10-6) between DM1 and DRB1 alleles encoding Lys71+. Family-based association studies showed that DRB1Lys71+ was the most important determinant of DM1 in carriers (haplotype relative risk = 8.38). Haplotype analysis confirmed this.
Conclusion: The DRB1Lys71+ allele confers genetic predisposition to DM1 most strongly of all.
Mohammad Hossein Niknam, Ali Rafinejad, Ali Akbar Amirzargar, Farideh Khosravi, Bagher Larijani,
Volume 3, Issue 2 (6-2004)
Abstract
Background: Type 1A Diabetes Mellitus (T1DM) is a chronic and progressive auto- immune disorder resulting from immune mediated destruction of Langerhans islet beta cells. The etiology of T1DM like the other autoimmune diseases is unknown and many factors are involved, Both humoral and cell-mediated immunity have a critical role in T1DM pathogenesis. The cytokines, the immunomodulatory peptides, are responsible for the immune cell recruitment and producing auto-antibodies by the immune effector cells. To evaluate the role of cytokines in sensitivity or resistance to T1DM, we have employed IFN gamma to determine their gene polymorphisms and their association with T1DM.
Methods: 30 patient suffering from T1DM and 40 normal control were studied simultaneously .PCR technique was used to characterize the polymorphisms of cytokine. Salting out method was performed for DNA isolation .The polymorphosime of IFN gamma gene was determined on position UTR+5664`5.The PCR products were evaluated by Gel Electerophoresis Technique.
Results: There was a significant difference between patient and control group in TT allele IFN gamma gene: p<0.05, RR: 0.39(0.22
Javad Tavakkoly Bazzaz, Vera Pravica, Andrew Jm Boulton, Ian V Hutchinson,
Volume 4, Issue 1 (7-2004)
Abstract
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.
Javad Tavakkoly Bazzaz, Vera Pravica, Andrew Jm Boulton, Ian V Hutchinson,
Volume 4, Issue 1 (7-2004)
Abstract
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.
Mahdi Zamani, Mohammad Amin Tabatabaiefar, Arezoo Savabi Esfahani, Fereidoon Mostafavi, Arya Sotoudeh, Bagher Larijani,
Volume 4, Issue 4 (6-2005)
Abstract
Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which T-cell mediated selective pancreatic β- cell destruction occurs. Half the risk of T1DM development is given by the HLA gene region while the remaining risk is assigned to non-HLA genes , probably those engaged in the formation of antigen interaction complex. The CD4 gene product, which is among the most prominent T-cell surface receptors with a key role in antigen processing, could be regarded as a strong candidate.
Methods: We investigated the possible association of the CD4 gene polymorphism with T1DM using the candidate gene approach. The pyrimidine- rich pentanucleotide repeat polymorphism residing in the promoter region of the CD4 gene was studied. In the present study 92 Iranian T1DM patients and 108 healthy matched control individuals were screened by PCR technique.
Results: The analysis of our results shows the protective association of CD4*A3 (RR= 0.159, 95% CI: 0.036-0.707 Pc=0.025) and the susceptible role of CD4*A5 (RR= 7.379, 95% CI: 1.630-33.414 Pc=0.010) with T1DM.
Conclusion: Our results suggest that the certain CD4 alleles are associated either negatively or positively with T1DM in the Iranian population.
Javad Tavakkoly Bazzaz, Vera Pravica, Andrew Jm Boulton, Ian V Hutchinson,
Volume 4, Issue 4 (6-2005)
Abstract
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.
Javad Tavakkoly Bazzaz, Vera Pravica, Andrew Jm Boulton, Ian V Hutchinson,
Volume 5, Issue 2 (9-2005)
Abstract
Background: Vascular factors in conjunction with metabolic issues are involved in both etiopathogenesis of diabetic neuropathy (DNU), and more remarkably in "repair" phase, when the net balance between neuroregenerative/degenerative reactions is dictated to some extent by these factors. The ischemic nature of DNU indicates the importance of re-establishment of blood vessels. VEGF, a growth factor which, in addition to its hemodynamic effects, possesses an "angiogenic" capacity has been the subject of extensive investigations in DNU, especially, interventional therapies. The impacts of racial and inherited backgrounds in the development of DNU suggest that the genetic issues partially govern the outcome of diabetic late complications, including DNU. By conducting a candidate gene case-control association study, present study explores the possibility if the inter-individual variations of VEGF gene structure by any means encode the genetic susceptibility/resistance in the course of DNU.
Methods: The distribution of VEGF gene polymorphisms frequencies were analyzed at positions –7*C/T, -1001*G/C, -1154*G/A and –2578*C/A and were evaluated by ARMS-PCR in 248 type 1 diabetic subjects (81 DNU+, 167 DNU−) and 113 healthy controls, all from "British-Caucasian" origin.
Results: When the frequency of the polymorphic alleles/genotypes between patients and controls, and also between two subgroups within patients' group with each other (DNU+ vs. DNU−) or with healthy controls were compared, only in one situation a significant difference was evident. The distribution of a VEGF gene polymorphism at promoter region (–7*C/T) at allelic (but not at genotypic) level was notably different between diabetics, with and without neuropathy, while the minor allele (T) conferred a protective effect (P=0.03 OR = 1.75).
Conclusion: The present study may imply a prognostic value for VEGF gene polymorphism at promoter region (–7*C/T) in DNU. However, it requires further studies to appreciate better the phenotypic impact of this polymorphism in this chronic complication of diabetes. A catalog of candidate genes polymorphisms that functionally reflect a protection/predisposition to DNU can provide the genotypic profile that can be useful to reasonably predict the overall behavior of diabetic subjects to the metabolic derangements relative to development of DNU, which in turn may require adoption of relevant preventive and therapeutic measures.
Javad Tavakkoly Bazzaz, Vera Pravica, Andrew Jm Boulton, Ian V Hutchinson,
Volume 5, Issue 3 (5-2006)
Abstract
Background: VEGF is newly discovered growth factor that has diverse biologic properties. The bottom-line of these activities is conduction and orchestration of a series of reactions that are taking place at microvasculature of different tissues/organs. Among the growth factors, cytokines and other mediators that reflect meaningful alteration in their local/systemic level, VEGF is the distinct player which can explain by its own all hemodynamic and architectural manifestations present in diabetic retinopathy (DR). The present study was conducted to pursue the role of a candidate gene structure variation, VEGF gene polymorphisms, in genetic susceptibility/resistance to development of DR through a cross sectional case-control study.
Methods: The frequency of four SNPs in VEGF gene at positions –7*C/T, –1001*G/C, –1154*G/A and –2578*C/A has been traced among 248 type 1 diabetic subjects (135 DR+, 113 DR−) along with 95 healthy controls. The populations had "British-Caucasian" background and ARMS-PCR technique was employed for DNA genotyping.
Results: Comparing the polymorphic variants' frequency at both allelic and genotypic levels among different groups/subgroups, significant difference was noticeable for –7*C/T polymorphism between diabetic patients with vs. without DR, while T allele conferred protective effect (p=0.002 OR=1.98).
Conclusion: Contemplating that up-regulation/over-expression of VEGF (local/systemic) as a common pre-requisite for DR development, our hypothesis was that whether the VEGF gene structural variations is correlated with the magnitude of VEGF expression in response to different stimuli present in diabetic context, namely hypoxia and hyperglycemia. Our data indicate that among the examined polymorphisms of VEGF gene, only SNP at position –7*C/T harbored significant difference between DR+ vs. DR− cases, proposing phenotypic impact for that SNP illustrating by evolvement/impediment of DR. However, reminding the insubstantial role of genetic issues in development of DR relative to DN or DNU, replicating current hypothesis by providing larger sample size and also employing more polymorphic markers could shed more light on the subject of present study.
Javad Heidari, Seyed Mohammad Akrami, Ramin Heshmat, Parvin Amiri, Hossein Fakhrzadeh, Mohammad Pajouhi,
Volume 5, Issue 3 (5-2006)
Abstract
Background: Uncoupling protein-2 (UCP2), one of the mitochondrial transporter memborane protiens, is suggested as a contributor gene for obesity. A common G/A polymorphism in the UCP2 promoter region is associated with obesity and diabetes.
Methods: As a cross-sectional study, 75 healthy 25-64 years volunteers were randomly selected from Tehran University of Medical Sciences population Lab. DNA was exracted from blood samples then polymorphism and A & G Allel frequencies were determined via PCR and RFLP. The correlation between genotype and such clinical and biochemical parameters as BMI, serum cholesterol and TG was investigated. Results were compared with other similar surveys.
Results: The frequencies of the UCP2 -866G/A genotypes in 75 Iranian normal population were AA: 7 (9.4%), GA: 41 (54.6%), and GG: 27 (36%).
Conclusion: Significantly higher HDL cholesterol was detected in people with GG allele (P=0.02) as compared with GA and AA alleles. 866 UCP2 G/A genotype frequencies in our study were significantly different as compared with Japanese population but no with European studies that may emphasize on genetical similarity between Iranian and European Caucasians populations.
Hassan Mirzaei, Taghi Golmohammadi, Seyed Mohammad Akrami, Mahmood Doosti, Manochehr Nakhjavani, Ramin Heshmat, Parvin Amiri,
Volume 6, Issue 1 (8-2006)
Abstract
Background: Peroxisome Proliferators- Activated Receptor-Gamma2 (PPAR- γ2) is a nuclear receptor that regulates adipocyte differentiation, lipid metabolism and insulin sensitivity. The aim of this study was to evaluate the association of the Pro12Ala polymorphism at the PPAR- γ2 gene in Iranian population with obesity.
Methods: The genomic DNAs of the 156 subjects including obese and healthy isolated from EDTA whole blood. Pro12Ala polymorphism detected by Polymerase Chain Reaction – Restriction Fragment Length polymorphism (PCR-RFLP).
Results: In the obese group , one sample (1.3%) was as homozygote Ala/Ala genotype , 24 samples (30.8%) were Pro/Ala heterozygote and 53 samples (67.9%)as Pro/Pro genotype were identified . in the control group , one sample (1.3%) was as Ala/Ala genotype , 12 samples (15.4%) were Pro/Ala genotype and 65 samples (83.3%) were Pro/Pro genotype. allele frequencies of Ala in obese subjects (qAla=%16.7)were significantly different from those in control subjects (qAla=%8.9).
Conclusion: Our results revealed that Pro12Ala polymorphism in PPAR- γ2 gene associated with obesity in the Iranian population and presence Ala allele cause to significantly higher BMI and lower fasting blood sugar.
Shirin Hasani Ranjbar, Javad Tavakkoly Bazzaz, Parvin Amiri, Mahsa M.amoli, Bagher Larijani,
Volume 6, Issue 3 (5-2007)
Abstract
Background: Single nucleotide polymorphisms of Adiponectin gene have been associated with BMI, insulin sensitivity and type 2 diabetes, reportedly. In present study we performed a genetic association study for Adiponectin gene at position +45*T/G in type 2 diabetes and normal subjects of Tehran population.
Methods: Diabetic patients were selected from diabetes clinic and normal healthy control subjects aged between 25-64 years selected from zone 17 of Tehran. Adiponectin gene polymorphism was analyzed using PCR-RFLP method in normal healthy controls (N=70), obese diabetic patients (N=80) and non-obese diabetic patients (N=72).
Results: Frequency of TT genotype was 62.5% in non-obese diabetic patients and 78% in control group, that was statistically significant (TT vs TG+GG: P=0.02, OR=2.2, CI:0.98-5.00). There was also a significant difference for allele T and G frequencies when we compared between non-obese diabetic patients and controls group. The frequency of allele G was increased in non-obese diabetic (20.1%) patients compared to controls (12%) (P: 0.04 OR: 1.8 CI: 0.9-3.7).
Conclusion: This study showed TG and GG alleles of Adiponectin gene polymorphism at position +45*T/G are risk factors for development of diabetes mellitus while this effect is independent from BMI and obesity.
Javad Tavakkoly Bazzaz, Vera Pravica, Andrew Jm Boulton, Ian V Hutchinson,
Volume 6, Issue 4 (6-2007)
Abstract
Background: IFN-g is one of the most essential and fundamental player in initiation and development of T1DM. This mediator belongs to T Helper-1(Th1) class of cytokines and exerts stimulation and differentiation of naïve T cells towards Th1 cells and meanwhile inhibits differentiation and proliferation of Th2 cells. These effects are highly important in induction and progression of cell-mediated immune responses that is aberrantly operative in development of T1DM. Due to such outstanding role, numerous studies including genetic manipulation have focused on the role of this pro-inflammatory cytokine in T1DM.
Methods: In a genetic association study the influence of IFN-g gene variation in position +874*T/A on development of T1DM was analysed in 248 British Caucasian T1DM patients in comparison with 119 healthy matched controls. ARMS-PCR procedure was designed for detection of the variants at allele/genotype level.
Results: No significant association between IFN-g gene polymorphism and T1DM was apparent (P≥ 0.05). The distribution of these polymorphic variants was in Hardy-Weinberg equilibrium.
Conclusion: While some studies have shown an association between the examined polymorphism of IFN-g and T1DM, our data do not support that. According to present study the selected polymorphic marker (+874*T/A) is not among the polymorphisms that governs in part genetic susceptibility to T1DM. That irreproducibility or controversial results is a common observation in genetic studies of complex traits such as T1DM, reflecting a fragile correlation between genotype and phenotype. This study also underlines the importance of replication of association studies to confirm the previous results/interpretations.
Javad Tavakkoly Bazzaz, Vera Pravica, Andrew Jm Boulton, Ian V Hutchinson,
Volume 7, Issue 1 (7-2007)
Abstract
Background: The alteration of IGF-I systemic level in diabetes is typically characterized by depletion of free IGF-I plasma level and its decreased bioavailability. With regard to protective and advantageous effects of IGF-I on tissue healing and cellular regeneration such depletion could facilitate or accelerate tissue damages and complications. By contrast, the local concentration of IGF-I is reportedly increased in particular tissues during some occasions, which has also clinical implications as IGF-I could function in an autocrine and paracrine manner.
The present study was conducted to assess that whether the differential outcome of diabetic subjects relative to diabetic retinopathy (DR) is linked to some extent to the structural variations of IGF-I gene.
Methods: Two polymorphisms of the IGF-I gene at positions -383*C/T and -1089*C/T were employed for genotyping analysis by ARMS-PCR assay and the data of genotype/allele distribution was compared between two subgroups of 248 British Caucasian type 1 diabetic subjects, 135 cases with DR and 113 controls (DR-).
Results: The distribution of these polymorphisms did not associate significantly with presence or absence of DR (P≥ 0.05).
Conclusion: Since the involvement of IGF-I in development of DR is fairly rational, our results firstly may reflect some reservations about the functionality of the employed polymorphic markers and secondly may indicate that all regulators of IGF-I functionality or its local concentration level including IGFBPs and IGFRs should be taken into account, so their genes could be the subject of new study to accomplish current investigation.
Maryam Bahadori , Leila Kohan, Nosaybeh Jafari ,
Volume 14, Issue 2 (1-2015)
Abstract
Background: obesity is the major health problems affecting communities worldwide and the prevalence is rapidly rising. Obesity as a lifestyle-related factor increases the risk of many diseases. Omentin is a new adipocytokine that is abundantly expressed in visceral fat tissue and its expression levels reversely correlated with obesity. The purpose of this study was to investigate the association between Val109Asp genetic polymorphism of Omentin gene and obesity risk in women. Methods: This case - control study was done on 260 women, including 186 women with BMI<30 as a control group and 74 women with BMI&ge30 with obesity. Omentin genotypes were determined by the use of polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). The data were analyzed using the computer software SPSS for windows version17. Results: Genotype frequencies of the Asp/Asp, Asp/Val and Val/Val in the control group were 65.6%, 31.7%, 2.7% and obese patients were 51.4%, 39.2%, 9.5%, respectively. Comparison of genotype frequencies in the two groups showed that women with Val/Val genotype in compare to Asp/Asp had greater risk for complications of obesity (OR: 4.5, 95%CI: 1.3-14.9, P: 0.01). Conclusion: There is significant association between Val109Asp polymorphism in omentin gene and obesity in Iranian women.
Maryam Sadat Daneshpour, Bahareh Sedaghatikhayat, Mehdi Hedayati, Fereidoun Azizi,
Volume 14, Issue 4 (5-2015)
Abstract
Background: The prevalence of non-communicable disorders such as metabolic syndrome (MetS) is high in developing countries. Metabolic syndrome is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density cholesterol (HDL) levels. The present review aims to discover the genetic variant reported in association with MetS. Methods: The database for genotypes and phenotypes (dbGaP) and the database for genetic associations and human genome (HuGE navigator) were utilized in order to search for genes and their corresponding polymorphisms related to MetS. Additionally, an electronic literature search for other Iranian studies and the genetic aspect of TLGS was completed using PubMed. Results: For phenotype selection in PheGenI, 30 traits were chosen and after the analysis, 21 of them were in common results with MetS. After finding the common variation between traits and MetS, omitting the repeated SNPs, 173 variations were remained. Finally, results distinguished six of the most important genetic regions found to have strong association with MetS. Conclusion: Identifying major genes that are responsible for the metabolic syndrome may improve the medical care for treating individuals with metabolic syndrome, and eventually may lead to personalized medicine in which treatment is tailored genetically to the patient’s needs. The present candidate regions is a respectable start to replicate genetic studies in large affected Iranian individual which we hope leads us to improve our medical care in this field.
Bita Faam, Asieh Zahedi, Mehdi Hedayati, Fereidoun Azizi, Mohammad Ali Mansournia, Maryam Daneshpour,
Volume 15, Issue 1 (1-2016)
Abstract
Background: The scavenger receptor class B type I (SR-BI), as the high density lipoprotein cholesterol (HDL-C) receptor, is a key component in the reverse cholesterol transportation. The objective of this study was to assess the association between exon1 (G→A) polymorphism of SR-BI gene and lipid profiles among the Tehran Lipid and Glucose Study (TLGS) population.
Methods: This cross-sectional study included 774 adults (322 males and 452 females) aged 20–70 years, who were randomly selected from among TLGS population. Anthropometrical and biochemical variables for participants were measured. Selected SR-BI gene polymorphism was determined with restriction fragment length polymorphism (RFLP) using the Alu restriction enzyme.
Results: according to the results of current study, in the Tehran population, the allele frequency of SR-BI (G→A) polymorphism was 0.159 for an allele (minor allele) and 0.841 for G allele. Allele frequencies were in conformity with Hardy–Weinberg equilibrium. The result of this study showed that Subjects with the less common allele (allele A), after adjusting for age, have lower HDL-CandHDL3concentrations (p=0.046, p=0.041 respectively).
Conclusion: lipid disorders are caused by the interaction of environmental and genetic factors; therefore, exon1 (G→A) polymorphism of SR-BI gene could not be the only cause for the abnormality in the HDL-C levels. In future, this polymorphism may be use as a molecular marker for diagnosis.
Maryam Mortezaee, Abbasali Raz, Shole Mansouri, Zohreh Annabestani, Zahra Mirzaeezadeh, Bagher Larijani, Mehrdad Hashemi, Kobra Omidfar,
Volume 15, Issue 5 (7-2016)
Abstract
Background: Insulin resistance and progressive β-cells failure are the key factors in type 2 diabetes mellitus (T2DM) pathogenesis. Many studies support a primary role of RBP4 in insulin resistance and suggest that genetic variations which alter the expression level of RBP4 might influence the risk of T2DM and its complications. Diabetic foot is one of the main complications of diabetes leading to disability and hospitalization. In addition, it reduces quality of life and imposes great cost to patients. The purpose of this study was to evaluate the correlation between two single nucleotide polymorphisms (rs10882273 and rs10882283) of RBP4 genes with diabetic foot ulcer in order to identify a biomarker for prediction of diabetic foot ulcer.
Methods: This is a case-control study. Two single nucleotide polymorphisms of RBP4 genes were genotyped by hit Tetra ARMS PCR technique. In this study, 100 and 133 diabetic patients with and without foot ulcer were selected as the cases and controls, respectively.
Results: The Chi-square test revealed no significant difference in frequency of TT, CC and TC alleles of rsl0882273 between case and control groups (P=0.414). Also, Comparison of AA, CC and AC alleles of rsl0882283 in both groups did not show significant difference (P=0.85).
Conclusion: According to this study, there is no relationship between two single nucleotide polymorphisms of RBP4 genes (rs10882273 and rs10882283) with diabetic foot ulcer in type2 diabetes patients.
Sharare Hassanzade, Abbasali Raz, Masoumeh Mansouri, Zahra Mirzaeezadeh, Bagher Larijani, Mehrdad Hashemi, Kobra Omidfar,
Volume 16, Issue 1 (1-2017)
Abstract
Background: Type 2 diabetes is a metabolic disorder characterized by high blood sugar levels that can damage nerves. Many organs are affected ،especially the foot that leading to loss of sensation. These factors make favorable conditions for the development of diabetic foot ulcers. Polymorphisms (Thr399Ile) of Toll Like Receptor4 (TLR4) gene due to malfunction of TLR4 protein which plays an important role in immunity. The purpose of this study was to determine the parameters which are affecting the imbalance resulting in chronic inflammation and wound healing. By showing the relationship between single nucleotide polymorphism (Thr399Ile) of TLR4 gene with diabetic foot ulcer we can identify a biomarker for prediction of diabetic foot ulcer.
Methods: This is a case-control study. Single nucleotide polymorphisms of TLR4 gene were genotyped by hit Tetra ARMS PCR technique. In this study, 100 and 120 diabetic patients with and without foot ulcer were selected as the cases and controls, respectively.
Results: The Chi-square test revealed significant difference in frequency of TT, CC and TC alleles of (Thr399Ile) between case and control groups (P=0.021).
Conclusion: According to this study, there is a relationship between single nucleotide polymorphisms (Thr399Ile) of TLR4 gene with diabetic foot ulcer in type 2 diabetes patients
Marzieh Arshadi Mashkani, Mahsa Mohammad Amoli, Iman Salahshorifar, Farideh Razi,
Volume 16, Issue 3 (3-2017)
Abstract
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
Saeedeh Asgarbeik, Mahsa Mohammad Amoli, Seyed Abdolhamid Angaji, Farideh Razi, Ensieh Nasli Esfahani,
Volume 16, Issue 3 (3-2017)
Abstract
Background: Diabetic Nephropathy is one of the main microvascular complications of diabetic mellitus. Methylenetetrahydrofolate Reductase (MTHFR) is one of the candidate genes of diabetic nephropathy. MTHFR (C677T) polymorphism reduces catalytic activity of MTHFR and leads to increase level of plasma homocysteine. The aim of this study was to evaluate the association of C677T polymorphism with diabetic nephropathy.
Methods: In this case control study, 300 individuals, including type 2 diabetes mellitus with diabetic nephropathy (N=104), diabetes mellitus patients without diabetic nephropathy (N=100) and controls (N=96) participated. The MTHFR genotype was determined using PCR-RFLP technique and biochemical parameters were measured.
Results: Genotype frequencies were significantly different between patients with diabetic nephropathy and diabetes mellitus without nephropathy (TT+CT vs CC; P=0.02,OR:0.5,CI:0.3-0.9).The allele frequency was also significantly different between diabetic nephropathy and diabetics mellitus without nephropathy(P=0.013,OR:1.754,CI:1.123-2.740).
Conclusion: These findings suggest that there is an association between C677T polymorphism and nephropathy in patients with type 2 diabetes. Allele C increase the risk of nephropathy, and T allele has a protective role in susceptibility to disease.
