Comparison of BRCA1 expression between triple-negative and luminal breast tumors

Background: Previous studies have suggested that BRCA1 dysregulation has been shown to have a role in triplenegative phenotypic manifestation. However, differences of BRCA1 expression, as a tumor suppressor gene, have rarely been investigated between luminal and triple-negative breast tumors. Therefore, the present study attempted to compare the BRCA1 expression in triple-negative with luminal breast tumors and its association with the clinicopathologic characteristics of patients

Methods: BRCA1 expression was evaluated by real-time PCR in 26 triple-negative and 27 luminal breast tumors

Results: The results revealed that there is a high frequency of BRCA1 underexpression in both triple-negative and luminal breast tumors. The BRCA1 underexpression was related to young age at diagnosis, lymph node involvement, and grade III tumors

Conclusion: The observations suggest that decreased BRCA1 expression, regardless of tumor subtype, has a general role in breast malignancy and associated with poor prognostic features in breast tumors

[Candidate gene analysis in diabetic retinopathy: eNOS gene]

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

[Genetics of type 1 diabetes: study of TNF-alpha gene]

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