Sex-based Dysregulation of Inflammation-related Genes in Periodontitis.

Periodontitis is a chronic inflammatory condition affecting a large population all over the world. This condition is linked with abnormal expression of numerous genes. We measured levels of CYFIP1, KDR, RABGGTA, RABGGTB and FOXD2 in gingival tissue and circulation of people with periodontitis and healthy controls. KDR was more expressed in tissue samples of female patients compared with female controls (Ratio of mean expression (RME) =4.16, P=0.02). However, this gene was less expressed in the blood of female patients compared with female control subjects (RME=0.12, P=0.04). RABGGTB was less expressed in the blood of male patients compared with male controls (RME=0.20, P=0.02). Finally, FOXD2 was less expressed in total blood samples compared with total controls (RME=0.3, P<0.001) and in blood samples of female patients compared with female control subjects (RME=0.02, P<0.001). RABGGTA had the best area under curve (AUC) value in differentiation of patients' tissues from normal tissues (AUC=0.60, sensitivity=0.37, specificity=0.92). In distinction of abnormal blood samples from controls, FOXD2 had the best performance (AUC=0.85, sensitivity=0.66, specificity=0.91). In brief, we demonstrated a sex-dependent dysregulation of KDR, RABGGTB and FOXD2 genes in circulation or tissue of patients with periodontitis.

Altered expression of SOCS genes periodontitis.

Suppressor of cytokine signalling (SOCS) family comprises a group of proteins that impede JAK/STAT signalling, thus being involved in the pathogenesis of immune-related conditions. In the present work, we aimed at identification of the role of SOCS genes in the pathogenesis of periodontitis through evaluation of their expression levels both in the circulation and in the affected tissues of patients. Thus, we measured expression levels of SOCS1-3 and SOCS5 transcripts in the blood and gingival samples of patients with periodontitis in comparison with control samples obtained during dental crown lengthening. Expressions of SOCS1, SOCS2, SOCS3 and SOCS5 genes were similar between gingival tissues of patients and controls. However, our results demonstrated under-expression of SOCS1 in blood samples of patients compared with controls (Ratio of mean expression (RME) = 0.47, P value = 0.04). The same pattern was observed among female subjects (RME = 0.38, P value = 0.04). SOCS2 was down-regulated in blood samples of female patients compared with female controls (RME = 0.22, P value = 0.04). SOCS3 was also under-expressed in the circulation of total cases versus total controls (RME = 0.29, P value = 0.02) and in female patients compared with female controls (RME = 0.19, P value = 0.04). Expression of SOCS5 was not different between blood samples two study groups. SOCS2 had the best function in separation of affected tissues from unaffected ones (AUC = 0.66, sensitivity = 0.39, specificity = 0.83). SOCS3 was superior to other transcripts in differentiation of blood samples of patients from normal blood samples (AUC = 0.69, sensitivity = 0.81, specificity = 0.68). Combination of transcript levels of SOCS1, SOCS2, SOCS3 and SOCS5 genes enhanced the AUC values to 0.64 and 0.67 in tissue and blood specimens, respectively. Taken together, certain SOCS genes have been found to be dysregulated in the circulation of patients with periodontitis.

Dysregulation of lncRNAs in circulation of patients with periodontitis: results of a pilot study.

BACKGROUND: Periodontitis is a chronic inflammatory disorder with a complex etiology. Long non-coding RNAs (lncRNAs) have been shown to affect pathoetiology of periodontitis. We aimed at identification of expression of five lncRNAs, namely Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 in the circulation and gingival tissues of these patients compared with healthy controls. METHODS: In a pilot case-control study, we compared expressions of Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 lncRNAs between blood and tissue samples of patients with periodontitis and healthy controls using real time quantitative PCR technique. The present work was performed on samples got from 26 patients with periodontitis and 28 controls. Female/male ratio was 16/10 and 12/16 in cases and controls, respectively. RESULTS: There was no significant difference in the expressions of Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 genes between affected and unaffected tissues. However, expressions of Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 genes were significantly lower in the blood samples of patients when compared with control samples (Ratio of mean expression = 0.16, 0.14, 0.13, 0.10 and 0.14, respectively). Subsequently, we compared expressions of these lncRNAs between patients and controls in a sex-based manner. Expressions of Linc00667, FENDRR and DIRC3 genes were significantly lower in female patients compared with female controls (RME = 0.09, 0.07 and 0.10, respectively). Yet, there was no significant difference in expression of any of mentioned lncRNAs among male subgroups. Consistent with the similar levels of Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 in tissue samples of patients and controls, none of them could separate these two sets of samples. However, AUC values for of Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 expression levels in blood samples were 0.66, 0.72, 0.70, 0.72, 0.70 and 0.68, respectively with FENDRR having the best sensitivity value. CONCLUSION: Taken together, lncRNAs might be involved in the pathologic events in the circulation of patients with periodontitis.

Over-Expression of Immune-Related lncRNAs in Inflammatory Demyelinating Polyradiculoneuropathies.

Long non-coding RNAs (lncRNAs) have crucial roles in the pathogenesis of immune-related disorders. However, their role in the pathobiology of inflammatory demyelinating polyradiculoneuropathies remains unclear. In the current study, we measured peripheral expression of four lncRNAs, namely TUG1, FAS-AS1, NEAT1, and GAS5, in patients with acute/chronic inflammatory demyelinating polyradiculoneuropathies (AIDP/CIDP) compared with healthy subjects. Notably, all lncRNAs were over-expressed in patients compared with controls (P < 0.0001 for all lncRNAs). When assessing their expressions in AIDP and CIDP groups separately, TUG1 and NEAT1 were up-regulated in both patient groups compared with controls, yet FAS-AS1 and GAS5 were only up-regulated in CIDP cases. There were remarkable pairwise correlations between expression levels of these lncRNAs in all study groups. Based on the above-mentioned data, we suggest participation of these for lncRNAs in the pathogenesis of inflammatory demyelinating polyradiculoneuropathies. Moreover, FAS-AS1 and GAS5 lncRNAs have type-specific roles in this regard. Future functional studies are needed to elaborate the molecular mechanisms of the contribution of these transcripts in AIDP/CIDP.

The rs4759314 SNP within Hotair lncRNA is associated with risk of multiple sclerosis.

Recent studies have demonstrated the role of long non-coding RNAs (lncRNAs) in the pathophysiology of autoimmune disorders such as multiple sclerosis (MS). Among these transcripts is HOX transcript antisense intergenic RNA (HOTAIR) whose contribution in MS has been verified both in animal models and in human studies. In the current study, we genotyped three single nucleotide polymorphisms (SNPs) with this lncRNA (rs12826786, rs1899663 and rs4759314) in 403 Iranian MS patients and 420 healthy subjects. After correction of P values for multiple comparisons, the rs4759314 SNP was associated with risk of MS in allelic model (OR (95% CI)= 1.34 (1.08-1.67), adjusted P value=0.02). The other SNPs were not associated with risk of MS in any inheritance model. The C G A haplotype (rs12826786, rs1899663 and rs4759314, respectively) was less prevalent in cases compared with controls (OR (95% CI)= 0.73 (0.59-0.90), adjusted P value=0.03). The T G A haplotype was more common among cases compared with controls (OR (95% CI)= 1.58 (1.20-2.08), adjusted P value=0.01). Taken together, HOTAIR might be regarded as a risk locus for MS in Iranian population.