Association between methylene tetrahydrofolate reductase polymorphisms and risk of ischemic stroke.

Background: The methylene tetrahydrofolate reductase (MTHFR) is a folate-dependent enzyme which catalyzes the conversion of homocysteine to methionine. Two single nucleotide polymorphisms (SNPs) within this gene namely rs1801133 (C677T) and rs1801131 (A1298C) have been associated with elevated risk of ischemic stroke and total serum homocysteine in some populations.Aim: To assess associations between MTHFR SNPs and risk of ischemic stroke in Iranian population.Methods: In the current case-control study, we genotyped rs1801133 and rs1801131 SNPs in 318 Iranian patients with history of ischemic stroke and 400 age- and sex-matched controls using tetra-primer amplification refractory mutation system-polymerase chain reaction method.Results: The rs1801133 was significantly associated with risk of stroke in recessive model (OR (95% CI) = 1.89 (1.12-3.20), p = 0.03). The CT haplotype (rs1801131 and rs1801133, respectively) was significantly over-represented in patients compared with controls (OR (95% CI) = 1.71 (0.25-2.32), p = 0.002).Conclusion: Consequently, our data demonstrate contribution of MTHFR variants in risk of ischemic stroke in Iranian population.

The efficacy of interferon-beta therapy in multiple sclerosis patients: investigation of the RORA gene as a predictive biomarker.

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory neuronal damages and consequent disabilities. Episodic relapses of the disease which lead to brain lesions and irreversible neurological dysfunctions could be decreased by the interferon-beta (IFN-ß) therapy in most of the MS patients. However, the efficiency of the drug response is highly variable among patients and the precise mechanism of action of the IFN-ß is not clear. To investigate the role of RORA gene as a biomarker of patient's responsiveness, the present study have analyzed the frequency of two polymorphisms (rs4774388 and rs11639084) within this gene between responder (n = 105) and nonresponder (n = 65) groups of MS patients in comparison with 200 healthy controls. The tetra primers-Amplification Refractory Mutation System-PCR method was used for genotyping. The obtained result of the current study showed a significant association between nonresponsiveness and the rs4774388 in dominant model (p = 0.03). However, the allele and genotype frequencies of rs11639084 were not different between controls, nonresponder, and responder patients. In addition, the frequencies of the estimated haplotype blocks were not different between examined groups. The obtained results of the present study suggested the rs4774388 as a possible effective factor in determination of response to IFN-ß. However, further studies are needed to confirm the results in a larger sample size.

Altered cytokine levels and immune responses in patients with SARS-CoV-2 infection and related conditions.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic in early 2020. The infection has been associated with a wide range of clinical symptoms. In the severely affected patients, it has caused dysregulation of immune responses including over-secretion of inflammatory cytokines and imbalances in the proportion of naïve helper T cells, memory helper T cells and regulatory T cells. Identification of the underlying mechanism of such aberrant function of immune system would help in the prediction of disease course and selection of susceptible patients for more intensive cares. In the current review, we summarize the results of studies which reported alterations in cytokine levels and immune cell functions in patients affected with SARS-CoV-2 and related viruses.

The rs594445 in MOCOS gene is associated with risk of autism spectrum disorder.

Molybdenum cofactor sulfurase (MOCOS) gene encodes an enzyme which is involved in purine metabolism. Recent experiments have shown down-regulation of MOCOS in adult nasal olfactory stem cells of individuals with autism spectrum disorder (ASD). In the current study, we genotyped two single nucleotide polymorphisms (SNPs) within coding regions of MOCOS gene (rs594445 and rs1057251) in 406 ASD patients and 411 age and sex-matched controls. The A allele of the rs594445 SNP was more prevalent among ASD cases compared with controls (OR (95% CI) = 1.33 (1.07-1.64), adjusted P value = 0.02). This SNP was associated with risk of ASD in co-dominant (AA vs. CC: OR (95% CI) = 2.00 (1.22-3.23), adjusted P value = 0.04) and recessive (AA vs. CC + AC: OR (95% CI) = 1.86 (1.16-2.98), adjusted P value = 0.02) models. The other SNP was not associated with risk of ASD in any inheritance model. There was no LD between rs594445 and rs1057251 SNPs (D' = 0.03, r2 = 0.14). The C T haplotype (rs594445 and rs1057251, respectively) had a protective role against ASD (OR (95% CI) = 0.76 (0.62-0.92), adjusted P value = 0.02). Other estimated haplotypes distributed equally between cases and controls. Based on the results of current study, the rs594445 SNP might be regarded as a risk locus for ASD in Iranian population.

Role of NR3C1 and GAS5 genes polymorphisms in multiple sclerosis.

Introduction: Multiple sclerosis (MS) as a progressive chronic disease of the central nervous system (CNS) is characterized by demyelination and axonal loss. Results of genetic studies and clinical trials have proved a key role for the immune system in the pathogenesis of MS. Glucocorticoids (GR) are regarded as potent therapeutic compounds for autoimmune and inflammatory diseases which act through their receptors encoded by Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) gene. Meanwhile, the long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) interacts with GR through binding to the DNA-binding domain (DBD) region and reduces GR transcriptional activity.Methods: The purpose of our study was to evaluate the association between MS and polymorphisms within NR3C1 (rs6189/6190, rs56149945, rs41423247) and GAS5 (rs55829688) genes in 300 relapsing-remitting MS patients and 300 healthy subjects.Results: We demonstrated significant differences in distribution of genotype, allele and haplotype frequencies of rs6189, rs41423247 and rs55829688 between the study groups.Conclusion: Our data may suggest that rs6189, rs41423247 and rs55829688 are associated with the increased risk of MS development. Future studies are needed to verify our results in larger sample sizes and elaborate the underlying mechanisms for contribution of these variants in MS disease.

Origin of the Induced Pluripotent Stem Cells Affects Their Differentiation into Dopaminergic Neurons.

Neuronal differentiation of human induced pluripotent stem (iPS) cells, both in 2D models and 3D systems in vitro, allows for the study of disease pathomechanisms and the development of novel therapies. To verify if the origin of donor cells used for reprogramming to iPS cells can influence the differentiation abilities of iPS cells, peripheral blood mononuclear cells (PBMC) and keratinocytes were reprogrammed to iPS cells using the Sendai viral vector and were subsequently checked for pluripotency markers and the ability to form teratomas in vivo. Then, iPS cells were differentiated into dopaminergic neurons in 2D and 3D cultures. Both PBMC and keratinocyte-derived iPS cells were similarly reprogrammed to iPS cells, but they displayed differences in gene expression profiles and in teratoma compositions in vivo. During 3D organoid formation, the origin of iPS cells affected the levels of FOXA2 and LMX1A only in the first stages of neural differentiation, whereas in the 2D model, differences were detected at the levels of both early and late neural markers FOXA2, LMX1A, NURR1, TUBB and TH. To conclude, the origin of iPS cells may significantly affect iPS differentiation abilities in teratomas, as well as exerting effects on 2D differentiation into dopaminergic neurons and the early stages of 3D midbrain organoid formation.

MALAT1 Genomic Variants and Risk of Multiple Sclerosis.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA (lncRNA) with a possible role in the regulation of immune responses. A previous study has demonstrated down-regulation of this lncRNA in multiple sclerosis (MS) patients. In the current study, we genotyped two MALAT1 single nucleotide polymorphisms (SNPs) in 428 Iranian MS patients and 505 healthy subjects. The G allele of the rs619586 was significantly under-represented in MS patients compared with controls (OR (95% CI) = 0.65 (0.46-0.92), adjusted P value = 0.03). This SNP was associated with lower MS risk in dominant model (OR (95% CI) = 0.63 (0.43-0.91), adjusted P value = 0.03). The rs3200401 was not associated with MS risk in any inheritance model. Moreover, the A T haplotype (rs619586 and rs3200401, respectively) within MALAT1 was associated with MS risk. The current study provides additional evidences for contribution of MALAT1 in the pathogenesis of MS.

Genetic variants within Ninjurin 2 gene are associated with risk of ischemic stroke in Iranian population.

Previous genetic and epidemiological studies have shown the contribution of genetic factors in conferring the risk of ischemic stroke. Among the acknowledged risk factors of stroke are the single nucleotide polymorphisms (SNPs) near Ninjurin 2 (NINJ2) gene which encodes a surface adhesion protein. In the current study, we investigated the role of two SNPs near this gene in ischemic stroke in Iranian population. The frequency of the A allele of the rs11833579 was significantly lower in cases compared with controls (OR (95% CI) = 0.68 (0.54-0.86), adjusted P value = 0.002). The rs11833579 was significantly associated with risk of stroke in co-dominant (AA vs. GG: OR (95% CI) = 0.39 (0.23-0.66), adjusted P value = 0.003) and recessive (OR (95% CI) = 0.44 (0.27-0.72), adjusted P value = 0.001) models. The rs3809263 was associated with risk of stroke in dominant model (OR (95% CI) = 1.5 (1.09-2.06), adjusted P value = 0.02). The A C haplotype (rs11833579 and rs3809263) decreased the risk of stroke (OR (95% CI) = 0.72 (0.57-0.91), adjusted P value = 0.03), while the G T haplotype conferred susceptibility to stroke (OR (95% CI) = 1.42 (1.11-1.82), adjusted P value = 0.02). Consequently, the present case-control study supports the role of NINJ2 as a risk locus for ischemic stroke in Iranian population.

A single nucleotide polymorphism within Ninjurin 2 is associated with risk of multiple sclerosis.

Multiple sclerosis (MS) is a devastating inflammatory disease of the central nervous system (CNS) associated with loss of myelin sheaths. The role of Schwan cells in the remyelination of MS lesions has been documented. However, the detailed steps of this process are unknown. Ninjurin 2 (NINJ2) encodes an adhesion protein with high expression in Schwann cells adjoining the distal piece of injured nerve. Based on the role of this protein in neurite outgrowth, it might participate in the process of nerve regeneration after nerve damage. In the present study, we genotyped two NINJ2 single nucleotide polymorphisms (SNPs) namely rs11833579 and rs3809263 in a population of Iranian patients with MS as well as healthy individuals. The frequency of T allele of the rs3809263 was significantly higher in MS patients compared with healthy subjects (OR (95% CI) = 1.33 (1.08-1.63), adjusted P value = 0.01). TT genotype of this SNP was associated with MS risk compared with CC genotype (OR (95% CI) = 2.22 (1.37-3.57), adjusted P value = 0.009). Moreover, the rs3809263 was associated with MS risk in recessive model (OR (95% CI) = 2.09 (1.33-3.31), adjusted P value = 0.003). There were no significant difference in the alleles and genotypes frequencies of rs11833579 between cases and controls. The current research suggests contribution of NINJ2 in the pathogenesis of MS and warrants further studies for elaboration of the underlying mechanism of such contribution.

GRM7 polymorphisms and risk of schizophrenia in Iranian population.

The role of metabotropic glutamate receptors in the pathogenesis of schizophrenia or response to antipsychotic treatment has been proposed previously. The aim of the current study was to investigate the associations between two intronic variants within GRM7 gene (rs6782011 and rs779867) and schizophrenia in Iranian population. These two single nucleotide polymorphisms (SNPs) were genotyped in 273 schizophrenic patients and 300 age and sex-matched normal controls. The frequency of A allele of the rs779867 was significantly lower in the schizophrenic patients compared with healthy subjects (OR (95% CI) = 0.71 (0.56-0.89), adjusted P value = 0.008). This SNP was associated with schizophrenia in co-dominant and dominant models (adjusted P values of 0.03 and 0.02 respectively). However, there was no difference in allele and genotype frequencies of the rs6782011 SNP between cases and controls. Consequently, the results of current study further highlight the participation of GRM7 in the pathogenesis of schizophrenia.

Soluble Receptor for Advanced Glycation End Products (sRAGE) is Up-Regulated in Multiple Sclerosis Patients Treated with Interferon ß-1a.

BACKGROUND/AIMS: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Considering the role of immune system in its pathogenesis, researchers have focused on evaluation of the expression of immune-related genes or proteins in MS patients. Among proteins whose participation in inflammatory process has been documented is the receptor for advanced glycation end products (RAGE). METHODS: In the present study, we compared RAGE transcript levels by means of quantitative real-time PCR as well as the serum level of soluble RAGE (sRAGE) by means of enzyme- linked immunosorbent assay (ELISA) in 50 IFNß-1a responsive relapsing-remitting MS patients when compared with age and sex-matched healthy subjects. RESULTS: Elevated expression of RAGE as well as higher levels of sRAGE were detected in IFN-ß responsive MS patients compared with the controls. A significant inverse correlation between sRAGE plasma concentrations and the expanded disability status scale (EDSS) was also detected in which each unit of increase in sRAGE level resulted in a 0.308 unit decrease in EDSS. CONCLUSION: Considering the stable clinical state of the MS patients in this study and their response to IFNß-1a, the elevated levels of sRAGE in patients compared with healthy subjects could be related to the effects of this kind of treatment.

Interleukin (IL)-8 polymorphisms contribute in suicide behavior.

Previous studies have highlighted the role of immune dysregulation in suicide behavior. Interleukin (IL)-8 is a chemokine with neuroprotective effects whose lower serum concentrations have been detected in individuals committed suicide. In the present study, we genotyped three single nucleotide polymorphisms (SNPs) within IL-8 gene (rs4073, rs2227306 and rs1126647) in 229 individuals who attempted suicide with soft suicide methods, 235 suicide victims and 290 individuals without any history of psychiatric disorders or suicide attempt. The T allele of rs4073 was significantly over-represented in suicide attempt group compared with both control and completed suicide groups (adjusted P values of 8.3E-7 and 9.8E-8 respectively). This SNP was associated with suicide attempt in both dominant and co-dominant models (P values of 6.2E-9 and 4.3 E-8 respectively). The genotype and allele frequencies of other SNPs were not significantly different among the three study groups. The T C A haplotype (rs4073, rs2227306 and rs1126647 respectively) were significantly less prevalent in completed suicide group compared with suicide attempt group (OR (95% CI) = 0.63 (0.46-0.86), adjusted P value = 0.03). Besides, the A T A haplotype has significant lower frequency in individuals who attempted soft suicide compared with controls (OR (95% CI) = 0.44 (0.26-0.75), adjusted P value = 0.02). However, this haplotype was significantly more prevalent in individuals attempted hard methods compared with those attempted soft methods (OR (95% CI) = 2.21 (1.26-3.87), adjusted P value = 0.04). The present study provided further evidence for the role of IL-8 in suicide behavior.

Cytokine profile in autistic patients.

The etiology of Autism Spectrum Disorders (ASDs) as severe neurodevelopmental ailments is not known. However, several evidences point to dysregulation of immune system as an underlying cause of ASD. In the present study we evaluated the mRNA expression levels of TNF-α, TGF-ß, IFN-γ, CXCL8, IL-1ß, IL-2, 1L-4, IL-6, IL-17 in whole blood samples of 30 ASD patients and 41 age and sex-matched healthy subjects with means of real-time PCR. TNF-α, IL-6 and IL-17 have been shown to be significantly up-regulated in ASD patients compared with healthy subjects (P < 0.0001, P = 0.001 and P < 0.0001 respectively). IL-2 has been shown to be significantly down-regulated in total ASD patients (P < 0.0001). No significant difference has been found in expression levels of other cytokines between patients and healthy subjects. The present study provides further evidences for dysregulation of immune response in ASD patients.

Cytoplasmic FMRP interacting protein 1/2 (CYFIP1/2) expression analysis in autism.

Cytoplasmic FMRP interacting proteins 1 and 2 (CYFIP1/2) have been previously shown to be associated with central nervous system (CNS) disorders such as autism spectrum disorder (ASD). Moreover, dysregulation of their expression levels results in disturbances in CNS maturation and neuronal interconnections. In the present study, we compared expression levels of CYFIP1/2 in peripheral blood of 30 ASD patients and 41 healthy subjects by means of real time PCR. Expression analysis showed significant over-expression of CYFIP1/2 in ASD patients compared with healthy subjects (Fold change = 3.252, P < 0.0001 and Fold change = 4.14, P = 0.001 respectively). Such over-expression was also seen for CYFIP1 in male and female patients when compared with the corresponding control subjects. In addition, a significant correlation was found between CYFIP1 transcript levels and age in female subjects. A significant correlation was detected between expression levels of these genes in control subjects. The current study provides further supports for contribution of CYFIP1/2 in the pathogenesis of ASD and potentiates it as a peripheral marker for ASD diagnosis. Future studies in larger sample sizes are needed to confirm the results of the current study.

Myxovirus resistance protein A (MxA) polymorphism is associated with IFNß response in Iranian multiple sclerosis patients.

Multiple sclerosis (MS) is a heterogeneous immune-related demyelinating disorder of central nervous system with several genetic and environmental factors contributing in its pathogenesis or patients' response to therapies. Myxovirus resistance protein A (MxA) is among the genes which are induced by IFNß and are involved in the MS pathogenesis and/or response to IFNß. In the present case-control study, we evaluated the association between three SNPs at nt -123 (A or C, rs17000900), nt -88 (G or T, rs2071430), and nt +20 (A or C, rs464138) and MS risk as well as treatment response in a population of Iranian MS patients including 146 IFNß responders and 85 non-responders as well as 180 healthy controls. The AGA (-123, -88, +20) haplotype was more frequent in controls compared with MS cases (P = 0.038, OR (95% CI) = 1.77 (1.03-3.02)). Of particular note, the frequency of rs464138 AA genotype was significantly higher in responders compared with non-responders. However, the allele and genotype frequencies of other SNPs were not significantly different among patient subtypes or between patients and controls. Besides, we have demonstrated that CGC, ATA, and AGA (-123, -88, +20) haplotypes were significantly associated with IFNß response in MS patients. As SNPs on MxA promoter region might participate in MS patients' response to IFNß, prior patients genotyping may increase the rate of responsiveness and help in individualized selection of treatment options.

Retinoic acid-related orphan receptor alpha (RORA) variants are associated with autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with various epidemiologic, genetic, epigenetic, and environmental factors being associated with it. The observed sex bias in ASD towards male has prompted investigators to propose sex-dependent mechanisms for ASD. Retinoic acid-related orphan receptor-alpha (RORA) is a new autism candidate gene that has been shown to be differentially regulated by male and female hormones. Previous studies have shown deregulation of its expression in the prefrontal cortex and the cerebellum of ASD patients. In the present study we aimed at identification of the possible associations between two functional polymorphisms in the RORA gene (rs11639084 and rs4774388) and the risk of ASD in 518 Iranian ASD patients and 472 age, gender, and ethnic-matched healthy controls by means of tetra primer-amplification refractory mutation system-PCR. The allele and genotype frequencies of rs11639084 were not significantly different between patients and controls. However, the allele frequencies of rs4774388 showed significant overrepresentation of T allele in patients compared with controls (P = 0.04, OR (95% CI) =1.21 (1.01-1.46)). The rs4774388-TT genotype was significantly higher in patients compared with controls and was associated with ASD risk in dominant inheritance model (P = 0.04, OR (95% CI) =0.77 (0.59-0.99)). Haplotype analysis showed significant association of two estimated blocks of rs11639084/ rs4774388 with ASD risk. Consequently, the present data provide further evidence for RORA participation in the pathogenesis of ASD.

Ras-like without CAAX 2 (RIT2): a susceptibility gene for autism spectrum disorder.

Ras-like without CAAX2 (RIT2) which encodes a GTP-binding protein has recently been reported as a new susceptibility gene for Autism Spectrum Disorders (ASD) in a genome-wide association study. Since the gene is suggested to be involved in the pathogenesis of different neurological diseases, we investigated the association of two single nucleotide polymorphisms (SNP) rs16976358 and rs4130047 of this gene with ASD in Iranian patients. A total of 1004 individuals, comprising 532 ASD cases and 472 healthy subjects participated in this study. Allele frequency analyses showed significant over-presentation of rs16976358-C allele in cases versus controls (P < 0.0001). In addition, rs16976358 CC genotype (OR (95% CI) =3.57(1.72-7.69) and P < 0.0001) and rs4130047 CC genotype (OR (95% CI) =0.64(0.43-0.97) and P = 0.035) were associated with ASD in recessive inheritance model. Besides, haplotype analysis demonstrated an association between the C/T haplotype block (rs16976358/rs4130047) and ASD (OR (95%CI) = 0.44 (0.31-0.62), P < 0.0001). Altogether, our findings provided additional confirmation for the RIT2 gene participation in ASD risk and suggested the rs16976358 variant as a possible genetic risk factor for this disorder.

Analysis of epigenetic clocks links yoga, sleep, education, reduced meat intake, coffee, and a SOCS2 gene variant to slower epigenetic aging.

DNA methylation (DNAm) clocks hold promise for measuring biological age, useful for guiding clinical interventions and forensic identification. This study compared the commonly used DNAm clocks, using DNA methylation and SNP data generated from nearly 1000 human blood or buccal swab samples. We evaluated different preprocessing methods for age estimation, investigated the association of epigenetic age acceleration (EAA) with various lifestyle and sociodemographic factors, and undertook a series of novel genome-wide association analyses for different EAA measures to find associated genetic variants. Our results highlighted the Skin&Blood clock with ssNoob normalization as the most accurate predictor of chronological age. We provided novel evidence for an association between the practice of yoga and a reduction in the pace of aging (DunedinPACE). Increased sleep and physical activity were associated with lower mortality risk score (MRS) in our dataset. University degree, vegetable consumption, and coffee intake were associated with reduced levels of epigenetic aging, whereas smoking, higher BMI, meat consumption, and manual occupation correlated well with faster epigenetic aging, with FitAge, GrimAge, and DunedinPACE clocks showing the most robust associations. In addition, we found a novel association signal for SOCS2 rs73218878 (p = 2.87 × 10-8) and accelerated GrimAge. Our study emphasizes the importance of an optimized DNAm analysis workflow for accurate estimation of epigenetic age, which may influence downstream analyses. The results support the influence of genetic background on EAA. The associated SOCS2 is a member of the suppressor of cytokine signaling family known for its role in human longevity. The reported association between various risk factors and EAA has practical implications for the development of health programs to improve quality of life and reduce premature mortality associated with age-related diseases.

Introduction of a multiplex amplicon sequencing assay to quantify DNA methylation in target cytosine markers underlying four selected epigenetic clocks.

BACKGROUND: DNA methylation analysis has proven to be a powerful tool for age assessment. However, the implementation of epigenetic age prediction in diagnostics or routine forensic casework requires appropriate laboratory methods. In this study, we aimed to compare the performance of large-scale DNA methylation analysis protocols that show promise in terms of accuracy, throughput, multiplexing capacity, and high sensitivity. RESULTS: The protocols were designed to target a predefined panel of 161 genomic CG/CA sites from four known estimators of epigenetic age-related parameters, optimized and validated using artificially methylated controls or blood samples. We successfully targeted 96% of these loci using two enrichment protocols: Ion AmpliSeq™, an amplicon-based method integrated with Ion Torrent S5, and SureSelectXT Methyl-Seq, a hybridization-based method followed by MiSeq FGx sequencing. Both protocols demonstrated high accuracy and robustness. Although hybridization assays have greater multiplexing capabilities, the best overall performance was observed for the amplicon-based protocol with the lowest variability in DNA methylation at 25 ng of starting DNA, mean observed marker coverage of ~ 6.7 k reads, and accuracy of methylation quantification with a mean absolute difference between observed and expected methylation beta value of 0.054. The Ion AmpliSeq method correlated strongly with genome-scale EPIC microarray data (R = 0.91) and showed superiority in terms of methylation measurement accuracy. Method-to-method bias was accounted for by the use of linear transformation, which provided a highly accurate prediction of calendar age with a mean absolute error of less than 5 years for the VISAGE and Hannum age clocks used. The pace of aging (PoAm) and the mortality risk score (MRS) estimators included in our panel represent next-generation clocks, were found to have low to moderate correlations with the VISAGE and Hannum models (R < 0.75), and thus may capture different aspects of epigenetic aging. CONCLUSIONS: We propose a laboratory tool that allows the quantification of DNA methylation in cytosines underlying four different clocks, thus providing broad information on epigenetic aging while maintaining a reasonable number of CpG markers, opening the way to a wide range of applications in forensics, medicine, and healthcare.

Emerging Role of Non-coding RNAs in Autism Spectrum Disorder.

Autism spectrum disorders (ASD) embrace a diverse set of neurodevelopmental diseases with a multifaceted genetic basis. Non-coding RNAs (ncRNAs) are among putative loci with critical participation in the development of ASD. Expression of some lncRNAs, namely RP11-466P24.2, SYP-AS1, STXBP5-AS1, and IFNG-AS1 has been decreased in ASD, while AK128569, CTD-2516F10.2, MSNP1AS, RPS10P2-AS1, LINC00693, LINC00689, NEAT1, TUG1, and Shank2-AS lncRNAs have been over-expressed in ASD. Expression of several miRNAs which are implicated in the immunological developmental, immune responses, and protein synthesis as well as those participating in the regulation of PI3K/Akt/mTOR and EGFR signaling pathways is dysregulated in the context of ASD. In the present article, we describe investigations which appraised the role of lncRNAs, miRNAs, and circRNAs in the pathobiology of ASD.