Showing 10 results for Genetic
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.
Bagher Larijani, Farzaneh Zahedi, Fariba Asghari,
Volume 4, Issue 0 (2-2005)
Abstract
Background: While the results of genetic research have increased our medical knowledge, promoted health and treatment of illness, some unique ethical problems arise about this type of research. Genetic information is often considered "special", or different from other kinds of medical information because of its close association with individual identity, which is due in part to the common assumption that genes are determinative of human health and characteristics. Thus there is potentially risk of harmful events genetic research participants including stigmatization or discrimination by employers and insurers. In addition, the fact that genetic information about an individual reveals information about relatives, creates new and complex ethical issues, particularly regarding privacy and confidentiality.
Methods: Given the importance of this subject, we searched PubMed, Medline and Ovid for some keywords such as "genetic research" and "ethics" during the recent decade. We compiled the article by reference to valid searched articles and some books.
Results & Conclusion: Informed consent, confidentiality, ownership of genetic information, family/cultural considerations, storage and future use of genetic samples, counseling and supervision contrivances are some respect important general ethical concerns which this paper discuss about briefly
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.
Seyed Mohammad Akrami,
Volume 6, Issue 3 (5-2007)
Abstract
Basic sciences attract specific attention of medical professionals worldwide. Medical genetics can bridge between clinical observations and basic sciences via specific focus on the molecular aspects of diseases. Importance of genetic counseling as the main part of management of inherited disorders should be realized by all physicians. This paper provides genetic counseling essentials with main focus on the endocrinopathies and metabolic disorders especially diabetes mellitus and its complications. This paper may help the endocrinologists to have more attention on these rules for referring rare familial or syndrome cases. High ethnicity variations and high rate of consanguineous marriage in Iran as well as increase in the incidence and prevalence of such disorders highlight the importance of molecular studies of such disorders in our country.
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.
Zahra Moradi, Mehrnaz Sadat Ravari, Effat Farrokhi, Morteza Hashemzadeh Chaleshtori,
Volume 19, Issue 1 (1-2020)
Abstract
Background: Type II diabetes is a chronic inflammatory condition that is associated with a combination of genetic and environmental factors. Tumor necrosis factor alpha or TNF-α as an adipocyte cytokine, which affects the signaling pathway of insulin, can contribute to insulin resistance in type 2 diabetes patients. Considering the importance of epigenetic changes in multifactorial diseases, this study aimed to investigate TNF-α promoter methylation in patients with type 2 diabetes.
Methods: This study was performed on 61 patients with type 2 diabetes and 31 non-diabetic patients. The Groups were matched in terms of demographic characteristics. The lipid profiles were measured by standard kits. TNF-α promoter methylation levels were measured by bisulphite treatment method, Nested PCR and sequencing.
Results: There was no association between TNF-α promoter methylation gene promoter and type 2 diabetes in the studied groups. Also, there was no association between TNF-α promoter methylation in diabetic and non-diabetic groups between males and females.
Conclusion: The epigenetic changes in cytokines that contribute to insulin resistance in type 2 diabetic patients seem to be ineffective in peripheral blood samples, and other tissues may need to be investigated in this regard.
