Search

Periodontitis is a complex disorder that affects a large number of human beings from different ethnic groups. This condition has been associated with dysregulation of a number of genes, among them are long noncoding RNAs (lncRNAs). In the current study, we assessed the expression of four lncRNAs (BDNF-AS, MIAT, MIR137HG, and PNKY) as well as BDNF in the peripheral blood and gingival tissues obtained from patients with periodontitis and healthy subjects. The expression of BDNF was significantly lower in blood samples of male patients with periodontitis compared with male controls (posterior β of RE = -4.754, p = .048). However, there was no significant difference in the expression of BDNF in tissue samples from the cases and controls. The expression of BDNF-AS was significantly lower in the tissue samples of patients compared with control tissue samples (posterior β of RE = -2.151, p = .019). Such an expression difference was detected between male subgroups as well (posterior β of RE = -3.679, p = .009). However, expression of this lncRNA was not different in blood samples obtained from patients compared with healthy subjects. The expression of PNKY was significantly higher in tissue samples obtained from female patients compared with sex-matched controls (posterior β of RE = 6.23, p = .037). Blood levels of this lncRNA were not different between cases and controls. There was no significant difference either in the tissue expression or in blood expression of MIR137HG or MIAT between cases and controls. The current study indicates the putative role of BDNF, BDNF-AS, and PNKY in the pathophysiology of periodontitis and potentiates these genes as candidates for functional studies.

The protein inhibitors of activated STAT (PIAS) are involved in regulation of many transcription factors and signaling pathways that contribute to the pathogenesis of bipolar disease (BD). In the current study, we evaluated the expression of four PIAS genes (PIAS1-4) in peripheral blood of BD patients and healthy subjects to explore their contribution in the pathogenesis of BD and their suitability as peripheral biomarkers for this disorder. All PIAS genes were significantly upregulated in total BD patients compared with total controls. The sex-based analysis confirmed upregulation of PIAS1-4 genes in male BD patients compared with male controls (P < 0.001). However, PIAS1 was significantly downregulated in female patients compared with female controls (P = 0.02). Expression levels of other PIAS genes were not significantly different between female patients and female controls. There were no significant correlations between expression levels of PIAS genes and any of the clinical data of study participants after adjustment of the effects of the sex. On the basis of the area under the curve (AUC) values in receiver operating characteristic curves, PIAS4 had the best performance in the differentiation of disease status between study participants (AUC = 0.81). PIAS3 and PIAS4 genes had the best sensitivity and specificity values, respectively. Combination of expression levels of four genes resulted in the improvement of diagnostic power (AUC = 0.82). The current data implies the role of PIAS genes in the pathogenesis of BD and denotes their suitability as peripheral markers for this disorder.

Multiple sclerosis (MS) is a devastating autoimmune disease of the central nervous system associated with demyelination and axonal injury. This study was designed to find potential lncRNAs and their targets that are associated with the molecular basis of MS pathogenesis. In this study, peripheral blood samples were obtained from 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls. lncRNAs and their target were selected for validation using TaqMan Real-Time PCR. Interactions were studied based on approaches that used to investigation biological functions and signaling pathways affected by differentially expressed messenger RNAs (mRNAs). The results of this study indicate an increase in the expression of HUR1 (p = 0.0001), CPSF7 (p = 0.02), and reduction of CSTF2 expression (p = 0.04). Also, an increase in the expression of OIP5-AS1 (p = 0.01) was observed in men less than 30 years old. We performed a comparative analysis of the long noncoding RNAs (lncRNAs), and then we ranked them as candidate biomarkers according to a decreasing area under the receiver operating characteristic (ROC) curve (AUC) and plotted the results. Dysregulation of lncRNA expression has been linked to diseases. Further studies on the HUR1 gene can be used as diagnostic tools for the identification of high-risk individuals in families with a history of disease before, during, and even after treatment. Our data uncovered the expression profiles of lncRNAs and mRNAs in MS patients, which will help delineate the molecular mechanisms in MS pathogenesis. However, further studies need to determine the precise role of these genes in the pathological process in MS.

Hypoxia-inducible factors (HIFs) have been shown to be upregulated in tumor tissues and linked with tumor progression and metastasis in breast cancer. Among regulatory mechanisms for HIF expression is a natural occurring antisense named aHIF, which has been shown to be overexpressed in breast cancer and influence the level of the HIF-1α transcript. In the present study, we analyzed the expression of HIF-1α and aHIF in breast cancer tissues versus adjacent noncancer tissues (ANCTs) in relation with the clinical and biological behavior of the tumors. aHIF has been shown to be expressed in 67.4% of invasive ductal carcinoma samples, while none of ANCTs showed its expression. HIF-1α has been expressed in all of tumors and 90% of ANCTs. Comparison of HIF-1α expression level between tumor and ANCT tissues showed a total upregulation in tumor samples. No statistically significant association has been found between the level of HIF-1α expression in tumor samples and clinicopathologic and demographic characteristics such as age, tumor size, estrogen receptor status, progesterone receptor status, HER2/neu expression level, lymph node status, histological grade, and stage except for a weak correlation between HIF-1α expression and Ki-67 status. Besides, we could not detect any significant correlation between relative expression of HIF-1α and aHIF in tumor samples. Collectively, these data suggest that aHIF overexpression can be used as a potential biomarker in breast cancer. However, further studies are needed for the evaluation of its mechanism of action in regulation of HIF-1α expression in different pathological conditions. HIF-1α overexpression results in the upregulation of several genes that participated in cancer-associated pathways such as proliferation, angiogenesis, and glucose metabolism. We showed that HIF-1α is upregulated in breast tumor samples compared with adjacent noncancerous tissues. Its expression has been associated with Ki-67 status. Its natural occurring antisense is only expressed in tumor tissues. Thus, it can be used as a potential biomarker in breast cancer.

Autism spectrum disorder (ASD) as a synaptopathy is revealed to be pertained to aberrant glutamatergic neurotransmission. Glutamate receptor, metabotropic 7 (GRM7), a receptor coding gene of this pathway, is a new candidate gene for autism. The aim of this study was to examine if there is a relationship between genetic variants rs779867 and rs6782011 of GRM7 with ASD. The present research was designed as a population-based, case-control study including 518 ASD patients versus 472 control individuals. The results showed that the frequency of rs779867 G/G genotype was significantly higher in ASD patients compared to healthy controls (P = 0.0001). Also, the G allele of this SNP was found to be significantly more frequent in the patients than control group (P = 0.0001). Haplotype analysis exhibited significant association of two estimated block of rs6782011/rs779867 in ASD patients versus control group. We found higher significant frequency of GT haplotype and lower frequencies of AT and AC haplotypes in the patients group compared to healthy controls (P = 0.001, P = 0.006, and P = 0.05, respectively). Our study indicated that the rs779867 polymorphism is associated with ASD; thus, results of this study provide supportive evidence of association of the GRM7 gene with ASD. Autism Res 2016, 9: 1161-1168. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Summary The purpose of this case–control study was to evaluate the frequencies and potential genetic susceptibility of the −330 IL2 T and G alleles and HLA-DRB1*1501 allele in Iranian patients with multiple sclerosis (MS) compared to healthy controls. Two hundred and sixty Iranian patients with MS from medical genetics department of Sarem Women hospital were selected. Besides, 450 ethnically age- and sex-matched healthy individuals without personal or family backgrounds of autoimmune disorders were enrolled as a control group. All polymorphisms were analysed using RFLP-PCR technique. HLA-DRB1 genotyping was carried out by HISTO TYPE SSP high-resolution Kits according to the manufacturer's suggestions. The frequency of the T allele at the −330 IL2 polymorphism was significantly higher in patients with MS than controls (OR: 2.45, 95 CI: 1.9–3, P = 4 × 10−14). Moreover, the T/T genotype was more frequent in patients than in controls (51% vs. 30%). This study indicated that the −330 T IL2 allele and the T/T genotype were related to increased plasma concentration of IL2 and a higher risk of developing MS among Iranian patients. Carrying both the −330 T IL2 and the HLA, DRB1* 1501 alleles showed the most susceptibly effect to MS. Our data demonstrated −330 T IL2 allele provided major susceptibility to MS and HLA-DRB1* 1501 allele had an additive effect. In addition, it seems that studies with larger sample size are required to bring about more authentic results. Our findings suggest that IL2 gene polymorphisms influence the susceptibility to MS in Iranian patients.

Summary Type 1 Diabetes mellitus (T1D) is an autoimmune and multifactorial disease. HLA-DRB1 and DQB1 loci have the strongest association with T1D. This study aimed at investigating (i) susceptibility or protection of alleles, genotypes and haplotypes of HLA-DRB1 and DQB1 loci; and (ii) highly polymorphic amino acid residues of HLA-DRb1 and DQb1 in 105 Iranian T1D patients and 100 controls. The results indicated that DRB1*04:01, 03:01, D QB1*03:02, 02:01 a lleles, D RB1*