Assessment of Association between NINJ2 Polymorphisms and Suicide Attempts in an Iranian Population.

Suicidal behavior as a psychological problem with high public health burden is associated with a number of genetically determined risk factors. In the current study, we investigated the association between two polymorphisms within the NINJ2 gene and risk of suicide in an Iranian population. The study included 295 individuals who attempted suicide with soft suicide methods, 234 suicide victims and 410 normal controls. The rs11833579 SNP was associated with death from suicide in a codominant model in that the AG genotype decreased the risk of death from suicide compared with the GG genotype (OR (95% CI) = 0.49 (0.34-0.71), adjusted P value = 4e-04). This SNP was also associated with death from suicide in dominant (AG + AA versus GG: OR (95% CI) = 0.63 (0.46-0.87), adjusted P value = 0.011) and overdominant (AG versus GG + AA: OR (95% CI) = 0.49 (0.35-0.69), adjusted P value < 0.0001) models. In addition, this SNP was associated with soft suicide attempts in a codominant model (AG versus AA + GG: OR (95% CI) = 0.7 (0.5-0.98), adjusted P value = 0.02). The rs3806263 SNP was associated with death from suicide in allelic (A versus G: OR (95% CI) = 1.48 (1.17-1.88), adjusted P value = 0.002), codominant (AA versus GG: OR (95% CI) = 3.14 (1.89-5.21), adjusted P value < 0.0001), recessive (AA versus GG + AG: OR (95% CI) = 3.47 (2.15-5.61), adjusted P value < 0.0001), overdominant (AG versus AA + GG: OR (95% CI) = 0.62 (0.45-0.87), adjusted P value = 0.0092) and log-additive models (OR (95% CI) = 1.45 (1.15-1.83), adjusted P value = 0.0034). When comparing allele/genotype frequencies of this SNP between suicide victims and soft suicide attempters, significant associations were found in allelic, codominant, recessive and log-additive models. The AG haplotype (rs11833579 and rs3806263, respectively) was significantly less prevalent among suicide victims compared with controls (OR (95% CI) = 0.37 (0.26-0.52), adjusted P value < 0.0001). This haplotype was also less prevalent among suicide victims vs. soft suicide attempters (OR (95% CI) = 0.43 (0.31-0.61), adjusted P value < 0.0001). The GA haplotype (rs11833579 and rs3806263, respectively) was less frequent among suicide victims compared with controls (OR (95% CI) = 0.63 (0.45-0.89), adjusted P value = 0.0156). Finally, the AA haplotype was more prevalent among suicide victims compared with both controls (OR (95% CI) = 2.37 (1.56-3.6), adjusted P value = 0.0002) and soft suicide attempters (OR (95% CI) = 1.92 (1.32-2.78), adjusted P value = 0.0012). Thus, these two SNPs might be regarded as genetic determinants of suicide risk in Iranian populations. Further studies in different populations are needed to verify these results.

Assessment of expression of RELN signaling pathway in multiple sclerosis patients.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Nearly 85% of MS patients are recognized with relapsing-remitting MS (RRMS), a typical clinical course of disease which is distinguished by several episodes of relapses, separated by remissions of neurological impairment. Failure of repair mechanisms is a main factor in progression of neurological dysfunction in MS. Several lines of evidence suggest that Reelin (RELN) signaling pathway can contribute in the regulation of repair mechanisms in MS patients. In the present study, we assessed expression levels of RELN and Disabled-1 (DAB1), two key genes in RELN signaling pathway, in peripheral blood of 50 RRMS patients and 50 matched healthy subjects. RELN was significantly down-regulated in total MS patients, and total female patients compared with the matched controls. However, no statistically significant difference was found in DAB1 mRNA expression between MS patients and controls. Furthermore, considerable correlations were detected between expression levels of RELN and DAB1 in the patients group. There were no significant correlations between expression levels of genes and EDSS, disease duration or age at onset. Our study provides evidences for the role of RELN signaling pathway in the pathogenesis of MS. Further studies are required to clarify the exact clinical significance of this pathway in MS patients.

Assessment of functional variants and expression of long noncoding RNAs in vitamin D receptor signaling in breast cancer.

PURPOSE: Vitamin D receptor (VDR) signaling pathway is implicated in the pathogenesis of breast cancer. PATIENTS AND METHODS: We selected VDR-associated long noncoding RNAs (lncRNAs) through an in silico analysis of available microarray and RNA-sequencing data and assessed their expression in 75 breast tumor samples and their adjacent noncancerous tissues (ANCTs). We also genotyped two functional polymorphisms within VDR gene in all patients. RESULTS: VDR, MALAT1, and LINC00511 were significantly upregulated in tumoral tissues compared with ANCTs (fold change [FC] =1.85, P=0.03; FC =1.54, P=0.04; and FC =4.75, P=0.000, respectively). In patients younger than 55 years, significant associations were found between expression levels of both SNHG16 and LINC00511 genes and nuclear grade (P=0.03), expression of LINC00346 and tubule formation (P=0.01), expression of both SNHG16 and SNHG6 genes and family history of cancer (P=0.01 and 0.03, respectively), as well as expression of VDR and progesterone receptor status (P=0.03). We detected significant correlations between expression levels of VDR and SNHG16 in both tumoral tissues and ANCTs. The TT genotype of FokI polymorphism was associated with the higher expression levels of VDR. FokI variants were associated with expression levels of both MALAT1 and SNHG16 in ANCTs (P=0.01 and 0.03, respectively). CdxII variants were associated with expression levels of SNHG16 in ANCTs. A significant correlation was found between FC values of SNHG16 expression and vitamin D levels. CONCLUSION: The present study provides further evidence for the contribution of VDR signaling and the related lncRNAs in the pathogenesis of breast cancer and introduces some novel lncRNAs as putative molecules in the interactive functional network of VDR signaling in breast cancer.

Assessment of Protein Prenylation Pathway in Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a chronic inflammatory disorder with several genetic and environmental factors being implicated in its pathogenesis. Protein prenylation as one of the important posttranslational modifications of proteins has crucial role in immune system regulation. In the current case-control study, we compared expression of five genes coding for the different subunits of proteins implicated in protein prenylation in 50 Iranian MS patients with those of healthy subjects. No significant difference has been found in FNTA and PGGT1B expressions between cases and controls. Spearman correlation analysis between FNTA relative expression and disease duration showed significant correlation in male patients (r = - 0.671, P = 0.024) but not female patients (r = 0.253, P = 0.12). FNTB expression was significantly higher in MS patients compared with healthy subjects. Spearman correlation analysis between FNTB relative expression and disease duration showed significant correlation in male patients (r = -0.876, P = 0.004) but not female patients (r = 0.296, P = 0.06). RABGGTA was significantly upregulated in total MS patients, total male patients, female patients aged between 30 and 40 and male patients aged >40 compared with corresponding control groups. RABGGTB was significantly downregulated in total MS patients, total female patients, and female patients aged > 40 compared with corresponding control groups. Totally, we demonstrated dysregulation of protein prenylation pathway in MS patients compared with healthy subjects. Future studies are needed to find the clinical implication of this pathway in MS patients.