MTHFR Gene polymorphisms and susceptibility to Migraine Attacks

Background: Migraine consisting of migraine with aura [MA] and migraine without aura [MO] is a painful neurovascular disorder affecting approximately 16% of the general population. A combination of genetic and environmental factors is involved in the pathogenesis of migraine. The MTHFR enzyme is involved in homocysteine [Hcy] metabolism and it has been reported that 1298 A to C and 677 C to T mutations in the MTHFR gene are associated with an increased in plasma Hcy levels. Hcy is a highly reactive amino acid and causes endothelial injury. Because a plausible theory about vascular impairment in migraine, it is considered that mutations in MTHFR gene and folate metabolism are associated with migraine

Materials and Methods: in total, 75 patients with migraine [24 with MA and 51with MO] in accordance with the IHS criteria participated in this case-control study. Control group were 128 normal matched healthy subjecys who selected from same region without history of migraine or other neurologic disorder after interviewing and examining by a physician. Mean age at entry was 36.42+/-9.6 and 31.64+/-8.9 years old in migraine and control group respectively. MTHFR polymorphisms were investigated by PCR-RFLP

Results: genotypic results indicated that the prevalence of the MTHFR 677TT genotype in migraine subjects was higher than control [17.3% and 3.1% respectively, P<0.001]. Interestingly the risk of migraine was 6-fold higher in subjects possessing the MTHFR 677T homozygous variant [OR=6.5; CI95%: 2.03-20.76]. No significant difference in the prevalence of MTHFR A1298C genotypes was observed in migraine group when compared to controls [P>0.001]

Conclusion: it seems that MTHFR C677T is a potential genetic risk factor for migraine attacks, both in MA and MO subclasses in Iranian population. C677T and A1298C joint effect could amplify the potential influence of each SNPs

Intrathecal amylin and salmon calcitonin affect formalin induced c-fos expression in the spinal cord of rats

Amylin and Salmon Calcitonin belong to the calcitonin family of peptides and have high affinity binding sites in the rat spinal cord. The aim of this study was to characterize receptors for Amylin and Salmon Calcitonin functionally in the spinal cord of rats. We assessed the expression of c-Fos in response to intraplantar formalin in the lumbar regions of the spinal cord in conscious rats. Amylin [0.05 nmoles] or Salmon Calcitonin [0.005 nmoles] was administered intrathecally [i.t.] 10 minutes before the start of the formalin test. Antagonists were injected intrathecally 10 minutes before the administration of either of the peptides. Two hours after formalin stimulation, rats pretreated intrathecally by either Amylin or Salmon Calcitonin, showed lower numbers of c-Fos immunoreactive nuclei in their lumbar spinal cord as compared to rats pretreated with saline. These effects were reversed upon co-administration of either of the Amylin antagonists AC187 or rat amylin[8-37], but not rat alpha-CGRP[8-37] A few cells with c-Fos immunoreactivity were found in the lumbar spinal cord of rats two hours after i.t. injection of saline, Amylin and/or Salmon Calcitonin. However, Fos-like immunoreactivity was increased in the lumbar spinal cord two hours after i.t. treatment of either of the antagonists AC187 and rat amylin[8-37], when compared to saline treated rats. Both Amylin and Salmon Calcitonin inhibit formalin induced c-Fos expression in the rat lumbar spinal cord when administered intrathecally. Effects of the two peptides were possibly produced by undefined receptors

Expression status of UBE2Q2 in colorectal primary tumors and cell lines

Background: Activation of the ubiquitin-proteasome pathway in various malignancies, including colorectal cancer, is established. This pathway mediates the degradation of damaged proteins and regulates growth and stress response. The novel human gene, UBE2Q2, with a putative ubiquitin-conjugating enzyme activity, is reported to be overexpressed in some malignancies. We sought to investigate the expression levels of the UBE2Q2 gene in colorectal cell lines as well as in cancerous and normal tissues from patients with colorectal cancer

Methods: Levels of UBE2Q2 mRNA in cell lines were assessed by Real-Time PCR. Western blotting was employed to investigate the levels of the UBE2Q2 protein in 8 colorectal cell lines and 43 colorectal tumor samples

Results: Expression of UBE2Q2 was observed at the level of both mRNA and protein in colorectal cell lines, HT29/219, LS180, SW742, Caco2, HTC116, SW48, SW480, and SW1116. Increased levels of UBE2Q2 immunoreactivity was observed in the 65.11% [28 out of 43] of the colorectal carcinoma tissues when compared with their corresponding normal tissues. Difference between the mean intensities of UBE2Q2 bands from cancerous and normal tissues was statistically significant at P<0.001 [paired t test]

Conclusion: We showed the expression pattern of the novel human gene, UBE2Q2, in 8 colorectal cell lines. Overexpression of UBE2Q2 in the majority of the colorectal carcinoma samples denotes that it may have implications for the pathogenesis of colorectal cancer

Expression of UBE2Q2, a putative member of the ubiquitin-conjugating enzyme family in pediatric acute lymphoblastic leukemia

Acute lymphoblastic leukemia [ALL] is a cancer of the white blood cells most commonly found in childhood with a peak incidence at 2-5 years of age. The ubiquitin degradation pathway facilitates degradation of damaged proteins and regulates the growth and stress response. This pathway is activated in various cancers, including ALL. It has been previously reported that the newly characterized human gene UBE2Q2, a putative member of the ubiquitin-conjugating enzyme family, is over-expressed in the tumor mass and invasive epithelium in head and neck squamous cell carcinoma and breast cancer. Here, we have used quantitative reverse transcriptase polymerase chain reaction [RT-PCR] to assess expression of the UBE2Q2 gene in bone marrow samples of 20 children with ALL. Whole blood samples of 20 normal children were used as control specimens. RT-PCR revealed the expression of UBE2Q2 mRNA in 80% of the bone marrow samples from ALL patients as well as in 85% of leukemic normal peripheral blood cells. According to the results of quantitative RT-PCR, the levels of UBE2Q2 mRNA expression in the bone marrow cells of 11 out of the 20 children with ALL [55%] were significantly higher [> 2-47 fold] than those in blood cells of normal children. Our data suggest that the newly characterized human gene, UBE2Q2, may have implications for the pathogenesis of ALL and could be used for molecular diagnosis purposes in the future