ABSTRACT
Objective: Chromosomal translocations are among the most common mutational events in cancer development, especially in hematologic malignancies. However, the precise molecular mechanism of these events is still not clear. It has been recently shown that alternative non-homologous end-joining [alt-NHEJ], a newly described pathway for double-stranded DNA break repair, mediates the formation of chromosomal translocations. Here, we examined the expression levels of the main components of alt-NHEJ [PARP1 and LIG3] in acute myeloid leukemia [AML] patients and assessed their potential correlation with the formation of chromosomal translocations
Materials and Methods: This experimental study used reverse transcription-quantitative polymerase chain reaction [RT- qPCR] to quantify the expression levels of PARP1 and LIG3 at the transcript level in AML patients [n=78] and healthy individuals [n=19]
Results: PARP1 was the only gene overexpressed in the AML group when compared with healthy individuals [P=0.0004], especially in the poor prognosis sub-group. Both genes were, however, found to be up-regulated in AML patients with chromosomal translocations [P=0.04 and 0.0004 respectively]. Moreover, patients with one isolated translocation showed an over-expression of only LIG3 [P=0.005], whereas those with two or more translocations over-expressed both LIG3 [P=0.002] and PARP1 [P=0.02]
Conclusion: The significant correlations observed between PARP1 and LIG3 expression and the rate of chromosomal translocations in AML patients provides a molecular context for further studies to investigate the causality of this association
ABSTRACT
Cystic fibrosis [CF] is a multiorgan autosomal recessive disorder. As CF is highly heterogeneous in Iran and many mutations have a low frequency, routine molecular diagnostic methods are not very efficient. The use of highly polymorphic intragenic markers not only can facilitate phenotype prediction in prenatal diagnosis by gene tracking, but also can lead to the demonstration of possible associations between haplotypes and specific mutations. We determined IVS8 polyT and M470V polymorphisms in exon 10 of CFTR gene in this case-control study. Polymorphisms of IVS8 polyT in 53 patients with CF were referred to Amirkola children's Hospital of Babol University of Medical Sciences, 2007 to 2011 and 49 fertile healthy individuals were determined by reverse dot blot method. M470V polymorphism was analyzed by PCR-RFLP. In IVS8 polyT study, T7 was the most frequent allele in healthy individuals than patients with CF [respectively, 82.8% Vs. 77.2%]. T9 was more abundant in patients with CF than normal individuals [respectively, 21.7% Vs. 7.4%, P=0.005]. T9/T9 genotype was more frequent in patients than healthy individuals [respectively, 15.1% and 2%, P=0.032]. Study for M470V polymorphism showed that M/V was the most common genotype in normal individuals and patients with CF [respectively, 49% and 40.4%]. M-T9 haplotype was highly associated with the disease in both patients with CF and normal individuals [respectively, 19.1% and 2.4%, [P<0.001]. The allelic distribution and heterozygosity results suggest that both M470V and IVS8 polyT can be helpful in the prenatal diagnosis of CF in Northern Iranians with a positive family history of the disease
ABSTRACT
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. 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. 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]. 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