Different Gene Expression Patterns of IL-1 Family Members in Parkinson's Disease: Results from Bayesian Regression Model.

Parkinson's disease, the second most prevalent neurodegenerative disorder lacking a recognized etiology, is influenced by oxidative stress and alterations in inflammatory cytokine levels. This study aimed to investigate the expression levels of Interleukin(IL)1 receptor accessory protein (IL-1RAcP), IL1ß, IL1α, IL33, and IL36 genes in blood cells and serum IL-1ß levels in Parkinson's disease patients compared to healthy controls (HCs).I n this case-control study, 44 Parkinson's disease patients and 44 age- and sex-matched HCs were included. Gene expression levels were assessed using Quantitative Real-time PCR, and serum IL-1ß levels were measured via enzyme-linked immunosorbent assay. Advanced statistical analyses using the Bayesian regression model in R software were employed. Parkinson's disease patients exhibited elevated expression levels of IL-1RAcP and IL1ß genes  but decreased levels of IL1α, IL33, and IL36 compared to HCs. Age-based differences were not significant. Regarding gender, IL33 transcript levels were significantly higher in males, and serum IL-1ß levels were increased in patients. Subgroup analysis by gender indicated alterations in IL1ß and IL-1RAcP expression in both genders, while IL1α, IL33, and IL36 showed reduced expression only in males. Remarkably, only female patients displayed significantly higher serum IL-1ß levels than female HCs. These findings suggest that dysregulation of immune-related factors plays a crucial role in Parkinson's disease.

Evaluation of CD137 and CD137L Transcript Levels and the Serum sCD137 in Immune-mediated Polyneuropathy.

Background: Abnormal humoral and cellular immune responses have been reported in immune-mediated polyneuropathies. CD137, as a costimulatory molecule and a TNF receptor superfamily member, has been demonstrated to have a key role in the pathogenesis of many autoimmune as well as inflammatory disorders. Objective: To evaluate the transcripts levels of CD137, its ligand (CD137L), and the serum levels of soluble CD137 (sCD137) in patients with immune-mediated polyneuropathy. Methods: A total of 45 patients and 46 sex and age-matched healthy individuals were enrolled in the study. CD137 and CD137L transcript levels were assessed by the Real-Time PCR, and the serum level of sCD137 was measured using the ELISA technique. The Bayesian regression model was used for statistical analysis at the 0.05 significance level in R 4.1.0 statistical environment. Results: Transcript levels of the CD137 and CD137L were higher in polyneuropathy patients in comparison with the healthy subjects (P=0.006 for both). Conversely, the mean level of sCD137 was significantly lower in the sera of patients compared to the controls (P<0.001). Conclusion: Our findings point to the possible role of CD137 and CD137L in immune-mediated polyneuropathy pathogenesis. More investigations are required to clarify the exact contributions of the mentioned molecules to the pathogenesis of immune-mediated polyneuropathies.

Assessment of Expression of SOCS Genes in Acquired Immune-Mediated Polyneuropathies.

Acquired immune-mediated polyneuropathies are classified to some subtypes among them are acute and chronic inflammatory demyelinating polyradiculoneuropathies (AIDP and CIDP). These two conditions share some common signs and underlying mechanisms. Based on the roles of Suppressor of cytokine signaling (SOCS) genes in the modulation of immune system reactions, these genes might be involved in the pathogenesis of these conditions. We evaluated expression of SOCS1-3 and SOCS5 genes in the leukocytes of 32 cases of CIDP, 19 cases of AIDP and 40 age- and sex-matched controls using real time PCR method. The Bayesian regression model was used to estimate differences in mean values of genes expressions between cases and control group. Expression levels of SOCS1 and SOCS2 were significantly lower in male patients compared with controls. This sex-specific pattern was also observed for SOCS3 down-regulation. Based on the area under curve values in Receiver Operating Characteristics (ROC) curve, diagnostic powers of SOCS1, SOCS2, SOCS3 and SOCS5 genes in the mentioned disorder were 0.61, 0.73, 0.68 and 0.58, respectively. Expression of none of genes was correlated with age of enrolled cases. The current study shows evidences for participation of SOCS genes in the pathophysiology of acquired immune-mediated polyneuropathies.

Over-expression of IL-6 coding gene in the peripheral blood of migraine with aura patients.

Migraine is a common disorder which is placed among the top ten reasons of years lived with disability. Cytokines are among the molecules that contribute in the pathophysiology of migraine. In the current study, we evaluated expression levels of IL-6 coding gene in the peripheral blood of 120 migraine patients (54 migraine without aura and 66 migraine with aura patients) and 40 healthy subjects. No significant difference was detected in expression of IL-6 between total migraine patients and healthy controls (Posterior beta = 0.253, P value = 0.199). The interaction effect between gender and group was significant (Posterior beta =-1.274, P value = 0.011), therefore, we conducted subgroup analysis within gender group. Such analysis revealed that while expression of this gene is not different between male patients and male controls (Posterior beta =-0.371, P value > 0.999), it was significantly over-expressed in female patients compared with female controls (Posterior beta = 0.86, P= 0.002). Expression of IL-6 was significantly higher in patients with aura compared with controls (Posterior beta = 0.63, adjusted P value = 0.019). However, expression of this cytokine coding gene was not different between patients without aura and healthy subjects (Posterior beta = 0.193, adjusted P value = 0.281). Therefore, IL-6 might be involved in the pathophysiology of migraine among females and migraine with aura among both sexes.

Increased Levels of IL-34 in Acquired Immune-Mediated Neuropathies.

Interleukin (IL)-34 is ligand for the colony-stimulating factor (CSF)-1 receptor. This cytokine has fundamental roles the pathogenesis of a number of autoimmune and neurologic disorders. However, its role in the pathogenesis of acute and chronic inflammatory demyelinating polyneuropathies (AIDP and CIDP) has not been assessed yet. We measured serum levels of IL-34 33 CIDP cases, 16 AIDP cases, and 33 control subjects using commercial ELISA kits. IL-34 levels were significantly higher in both AIDP (44.87 ± 4.38) and CIDP (44.87 ± 4.38) groups compared with healthy subjects (30.10 ± 1.05) (P = 0.046 and P = 0.01, respectively). Differences between female subgroups were insignificant. However, levels of this cytokine were significantly higher in male subjects with CIDP compared with male controls (P = 0.042). Thus, levels of this cytokine might be regarded as biomarkers for these kinds of autoimmune disorders. Future studies are needed to verify these results and find the molecular mechanism of participation of IL-34 in the pathogenesis of AIDP/CIDP.

Evaluation of Interleukin-23 and JAKs/STATs/SOCSs/ROR-γt Expression in Type 2 Diabetes Mellitus Patients Treated With or Without Sitagliptin.

The production of interleukin-23 (IL-23) and the expression levels of related genes were evaluated in type 2 diabetes mellitus patients. The correlations between them were also determined. Thirty patients without sitagliptin (sitagliptin negative; SN), 30 patients with sitagliptin (sitagliptin positive; SP), and 30 healthy controls (HCs) were recruited. The level of IL-23 in the supernatant of anti CD3-activated peripheral blood mononuclear cells (PBMCs) was assessed using enzyme-linked immunosorbent assay. The expressions of IL-23, JAK1/JAK2/TYK2, STAT1/STAT3, ROR-γt, and SOCS1/SOCS3 in PBMCs were evaluated by real-time polymerase chain reaction. The production of IL-23 and the expressions of IL-23, JAK2, STAT3, and ROR-γt were observed to be enhanced in SN patients versus HCs, while the levels were decreased in SP patients versus SN patients (P < 0.05). SOCS1 and SOCS3 expressions were lower in SN patients than HCs, and their expressions were elevated in SP patients versus SN patients (P < 0.05). In SN patients, positive correlations between the IL-23 with fasting plasma glucose and HbA1c were observed, and JAK2/STAT3/ROR-γt were positively correlated with IL-23. JAK2, STAT3, and ROR-γt were positively related to each other and were negatively related to SOCS3. Enhanced IL-23/JAK2/STAT3/ROR-γt and reduced SOCS1/SOCS3 were found in SN patients. Sitagliptin may regulate the IL-23 and related gene expression.

Enhanced expression of TIGIT but not neuropilin-1 in patients with type 2 diabetes mellitus.

BACKGROUND: The aggressive T helper cell responses and regulatory T (Treg) cells dysfunction exist in type 2 diabetes mellitus (T2DM). The co-inhibitory T cell immunoglobulin and ITIM-domain (TIGIT), neuropilin-1 (Nrp-1), and the co-stimulatory CD226 play a critical role in the inhibition or activation of immune responses. In this project, the expression of TIGIT, CD226, Nrp-1, and their ligands, CD155 and semaphorin 3A (Sema-3A) were investigated in T2DM. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from 30 patients with T2DM, and 30 healthy controls (HCs). The frequencies of TIGIT and Nrp-1 on CD4+CD25hi Treg cells, CD4+CD25- responder T cells, total CD4+ T cells, and non-CD4+ cells were assessed using flow cytometry. The mRNA levels of TIGIT, CD226, Nrp-1, CD155, and Sema-3A were assessed by real-time PCR. RESULTS: The percentage and MFI of TIGIT on CD4+CD25hi T cells, CD4+CD25- T cells, total CD4+ T cells, and non-CD4+ cells were higher in patients versus HCs (p < 0.05 for all). The mRNA level of TIGIT was increased in patients compared with HCs (p = 0.003). No differences were observed in the expression of CD226, CD155, Nrp-1, and Sema-3A between the groups. CONCLUSIONS: The expression of TIGIT was enhanced in T2DM and the TIGIT axis could be considered as a new therapeutic purpose for the T2DM.

High Levels of Il-19 in Patients with Chronic Inflammatory Demyelinating Polyneuropathy.

Immune-mediated neuropathies include some specific types such as acute and chronic inflammatory demyelinating polyneuropathy (AIDP and CIDP). Previous studies have demonstrated abnormal cellular or humoral immune responses in these conditions. Although aberrant regulation of several cytokines have been reported in AIDP and CIDP, the significance of interleukin 19 (IL-19) in these conditions have not been elucidated yet. In the current study, we assessed serum levels of IL-19 in 12 CIDP patients (female/male ratio, 4/8), 9 AIDP patients (female/male ratio, 3/6), and 27 normal subjects (female/male ratio. 8/19) using commercial ELISA kits. Notably, we detected higher levels of this cytokine in CIDP patients (136.4 ± 8.57 ng/l) compared with both AIDP patients (93.89 ± 2.26 ng/l) and controls (83.78 ± 1.72 ng/l). However, the differences between AIDP patients and controls were not significant. The current study demonstrates the role of IL-19 in the pathogenesis of CIDP and potentiates this cytokine as a biomarker for this condition.

Assessment of IL-38 Levels in Patients with Acquired Immune-Mediated Polyneuropathies.

Acute and chronic inflammatory demyelinating polyneuropathy (AIDP and CIDP) are two types of immune-mediated neuropathies in which abnormal cellular or humoral immune responses have been observed. Although dysregulation of several cytokines has been detected in these disorders, expression of interleukin 38 (IL-38) has not yet been assessed in AIDP and CIDP. In the current study, we evaluated serum concentrations of this member of the IL-1 family of cytokines in 24 patients with CIDP, 13 patients with AIDP and 27 healthy subjects. We detected higher levels of IL-38 in CIDP patients compared with controls. When assessing study subgroups based on gender, there were no significant differences in IL-38 levels among the three female subgroups (P = 0.14). However, the difference among male subgroups was significant (P = 0.010). A Tukey test showed significant differences between male CIDP patients and male controls (P = 0.014). Considering the proposed anti-inflammatory role of IL-38, higher levels of this cytokine in CIDP might reflect the presence of a compensatory mechanism to reduce inflammatory processes in these patients. Further longitudinal assessment of this cytokine is need to test this hypothesis.

Assessment of expression profile of microRNAs in multiple sclerosis patients treated with fingolimod.

Fingolimod is an immunotherapeutic drug approved in certain countries as first-line therapy for relapsing-remitting multiple sclerosis (RRMS). The drug has been shown to alter the expression of several coding and non-coding genes. In the current study, we assessed the expression of miR-506-3p, miR-217, miR-381-3p, miR-1827, miR-449a and miR-655-3p in peripheral blood of patients with RRMS undergoing treatment with fingolimod compared with healthy controls. We also compared the expression of these miRNAs between fingolimod responders and non-responders to determine their relevance with regard to response to fingolimod. Expression of miR-381-3p was significantly higher in responders than in controls (RE difference = 3.903, P = 0.005), while expression of miR-655-3p was significantly lower in both responders and non-responders compared with controls (RE difference = -1.03, P = 0.014; RE difference = -1.41, P < 0.0001, respectively). No difference was found in the expression of other miRNAs between study subgroups. In addition, there was no significant difference in the expression of any miRNA between responders and non-responders. Although there were significant pairwise correlations between expression levels of all of the assessed miRNAs in controls, MS patients exhibited differences in correlation patterns. Expression of miR-381-3p was correlated with age in responders. However, expression of other miRNAs did not correlate with age in any study subgroup. The current study indicates a possible role for miR-655-3p and miR-381-3p in the pathogenesis of MS or possible effects of fingolimod on the expression of these miRNAs. Future studies are needed to verify these results in larger patient populations.

Evaluation of Expression of STAT Genes in Immune-Mediated Polyneuropathies.

Immune-mediated polyneuropathies are acquired conditions that can be categorized to acute and chronic forms based on the disease course. Although the basic mechanism of these conditions has not been clarified yet, genes that regulate immune responses are putative contributors in their development. In the current study, we assessed expression of signal transducer and activator of transcription (STAT)1-3 and STAT5a genes in peripheral blood of 51 patients and 40 healthy subjects. Expression of STAT1 was higher in female patients compared with female controls (Posterior Beta = 3.622, P = 0.044). The gender*group interaction was significant for this gene which indicates different direction of association in males and females. Expressions of other STAT genes were not different between cases and controls. The diagnostic power of STAT1 in female subjects was estimated to be 0.72 with sensitivity of 68.75% and specificity of 84.62%. There was no significant correlation either between expression of different STAT genes or between their expression and age of study participants. The current study potentiates STAT1 as a putative factor in the pathophysiology of acquired immune-mediated polyneuropathies in females and suggests conduction of further functional studies to elaborate the molecular mechanism of this contribution.

Sexual dimorphism in up-regulation of suppressors of cytokine signaling genes in patients with bipolar disorder.

BACKGROUND: Proteins encoded by Suppressors of cytokine signaling (SOCS) genes have critical roles in the regulation of immune responses. Meanwhile, several lines of evidence support the presence of immune dysfunction in bipolar disorder (BD) patients. METHODS: In the present study, we assessed expression levels of SOCS1-3 and SOCS5 genes in peripheral blood of patients with BD and healthy subjects. RESULTS: All SOCS genes were up-regulated in patients compared with healthy subjects. However, when comparing patients with sex-matched controls, the significant differences were observed only in the male subjects except for SOCS5 which was up-regulated in both male and female patients compared with the corresponding control subjects. Significant pairwise correlations were found between expression levels of genes in both patients and controls. Based on the area under curve values, SOCS5 had the best performance in the differentiation of disease status in study participants (AUC = 0.92). Combination of four genes increased the specificity of tests and resulted in diagnostic power of 0.93. CONCLUSION: Taken together, these data suggest a role for SOCS genes in the pathogenesis of BD especially in the male subjects. Moreover, peripheral expression levels of SOCS genes might be used as a subsection of a panel of diagnostic biomarkers in BD.

Nicotinamide nucleotide transhydrogenase expression analysis in multiple sclerosis patients.

Background: Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial redox-induced proton pump that links NADPH synthesis to the mitochondrial metabolic pathway. It also participates in the regulation of immune responses. A long non-coding RNA namely NNT-antisense 1 (NNT-AS1) has been shown to be transcribed from the same locus and exert anti-proliferative effects in some tissues. Methods: In the current study, we evaluated expression of NNT and NNT-AS1 in peripheral blood of 50 relapsing-remitting multiple sclerosis patients compared with healthy subjects. The difference in NNT expression was significant in only in male subjects aged over 50 when compared with the corresponding control subgroup. Results: For NNT-AS1, based on the results of Quantile regression and adjustment of the effects of age and sex as well as the interaction between sex and disease status, no significant difference was found between cases and controls. Moreover, NNT and NNT-AS1 expressions were correlated with age in controls and in female subjects respectively. Conclusion: Finally, we assessed correlations between expressions of these genes and detected significant pairwise correlations between transcript levels of NNT and NNT-AS1 genes in both cases and controls. The current study highlights a gender-specific role for NNT in the pathogenesis of MS.

Assessment of Apoptosis Pathway in Peripheral Blood of Autistic Patients.

Autism spectrum disorder (ASD) includes a number of severe neurodevelopmental disorders known by defects in social interaction, impaired verbal and non-verbal interactions, and stereotypic activities and limited interests. Dysregulation of apoptotic pathways have been demonstrated in brain tissues of affected individuals. In the present study, we evaluated expression levels of apoptosis-related genes and miRNAs in peripheral blood of ASD patients compared with healthy subjects. Transcript levels of BCL2, CASP8, and hsa-29c-3p were significantly lower in total ASD patients compared with total normal children (P values = 0.003, 0.002, and 0.01 respectively). When sex of study participants was considered in the analysis, the difference in transcript levels of these genes was significant only in male subjects. Peripheral expression of BCL2 and hsa-29c-3p had 100% sensitivity 92% specificity in ASD diagnosis. The diagnostic power of combination of transcript levels of these genes was estimated to be 78% based on the calculated AUC value. The present study provides evidences for dysregulation of apoptotic pathways in peripheral blood of ASD patients and suggests certain apoptosis-related genes as biomarkers in this regard.

Expression analysis of vitamin D receptor-associated lncRNAs in epileptic patients.

Vitamin D has been vastly acknowledged as a neuroactive steroid controlling neurodevelopment. As it exerts its functions through activation of vitamin D receptor (VDR), several studies have assessed the role of VDR in brain function. More recently, a number of long non-coding RNAs (lncRNAs) have been recognized that alter expression of VDR. In the current study, we evaluated expression of four VDR-related lncRNAs (LINC00511, LINC00346, SNHG6 and SNHG16) in peripheral blood of 40 epileptic patients and 39 healthy subjects using quantitative real time PCR method. The relative expression levels of SNHG16 and LINC00511 were higher in epileptic patients compared with healthy subjects. For SNHG16, the difference was only significant between male patients and male controls, while LINC00511 had the opposite pattern. The results of Quantile regression model showed significant associations between SNHG6 and SNHG16 expressions and gender (P values of 0.027 and 0.009 respectively). Significant correlations were detected between expression levels of SNHG6 and SNHG16 (r = 0.32, P = 0.004), SNHG6 and LINC00346 (r = 0.37, P = 0.001), SNHG16 and LINC00346 (r = 0.30, P = 0.007) as well as SNHG16 and LINC00511 (r = 0.29, P = 0.009). Expression of LINC00346 was inversely correlated with vitamin D levels only in male epileptic patients (r = -0.58, P = 0.011). Expression of SNHG6 was correlated with vitamin D levels in male controls but no other subgroups (r = 0.51, P = 0.044). Based on the results of ROC curve analysis, SNHG16 had the diagnostic power of 0.86 in male subjects. Taken together, the current study provides evidences for dys-regulation of VDR-related lncRNAs in epileptic patients. The clinical significance of these finding should be explored in future studies.

Expression Profile of Selected MicroRNAs in the Peripheral Blood of Multiple Sclerosis Patients: a Multivariate Statistical Analysis with ROC Curve to Find New Biomarkers for Fingolimod.

Multiple sclerosis (MS) as a chronic autoimmune disease of the central nervous system (CNS) has been associated with dysregulation of several genes including miRNAs. In the present study, we assessed transcript levels of seven miRNAs (miR-96-5p, miR-211-5p, miR-15a, miR-34a-5p, miR-204-5p, miR-501-5p, and miR-524-5p) in the peripheral blood of MS patients compared with healthy subjects in association with response to fingolimod treatment. Expression levels of miR-211-5p and miR-34a-5p were significantly decreased in MS patients compared with healthy subjects (P values of 0.002 and 0.47). While subgroup analysis showed downregulation of miR-211-5p in both fingolimod responders and non-responders, miR-34a-5p expression was only decreased in responders. Moreover, miR-204-5p was downregulated in non-responder male patients compared with male controls. The current study underscores the role of miRNAs in determination of response to fingolimod in MS patients.

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.

Serum cytokine profile in schizophrenic patients.

Schizophrenia is a chronic severe mental disorder in which immunologic imbalances have been reported. Some researchers have demonstrated dysregulation of cytokine levels in this mental disorder. Considering the possible role of cytokines in the pathogenesis or clinical course of schizophrenia, we assessed serum levels of IL-4, IL-10, IL-17A and IFN-γ in a homogenous sample of Iranian patients who were in remission under treatment with Clozapine compared with sex and age matched controls. There was a statistically significant difference in IL-4 levels between patients and healthy subjects (P= 0.023). IL-4 levels were 83% higher in cases than in control group. No significant group*gender interaction was detected suggesting the similar IL-4 levels between males and females in each study group. There was no statistically significant difference in IFN-γ levels between patients and healthy subjects, but IFN-γ levels were 70% higher in male compared with female group. No significant differences have been found in serum levels of other cytokines between cases and controls or between males and females. The higher levels of IL-4 in patients treated with Clozapine might be due to effects of this antipsychotic drug on immune responses. Future studies are needed to elaborate the exact underlying mechanism.

Effect of Extremely Low Frequency Electromagnetic Fields on Expression of T-bet and GATA-3 Genes and Serum Interferon-γ and Interleukin-4.

This study investigated the effect of various magnetic flux densities of extremely low frequency electromagnetic fields (ELF-EMF) on expression of T-box transcription factor (T-bet) and GATA binding protein-3 (GATA-3) genes in the spleen and thymus of rats injected with human serum albumin (HSA). Moreover, serum levels of interferon (IFN)-γ and interleukin (IL)-4 were evaluated at two phases, that is, prestimulation and poststimulation with HSA. Eighty rats were separated into five groups, and four groups were exposed daily to 50 Hz EMF of 1, 100, 500, and 2000 µT magnetic flux densities for 60 days. To activate the immune system, 100 µg HSA was intraperitoneally injected into each rat on days 31, 44, and 58 of the regimen. Splenic and thymic T-bet and GATA-3 messenger RNA (mRNA) expression on day 61 was evaluated by reverse transcription quantitative PCR. Serum IFN-γ and IL-4 (in blood on day 31 before HSA and again on day 61) levels were evaluated by enzyme-linked immunosorbent assay. Expression of T-bet and GATA-3 mRNA was decreased in the spleen in hosts exposed to densities of 1 and 100 µT. Serum IFN-γ and IL-4 levels were also significantly decreased in 100 µT-exposed rats, but only at the prestimulation phase. From these findings, it appears that (30 and 60 days) ELF-EMF exposure could suppress the expression of some key genes associated with T helper (Th) cells and on some of their associated functions, that is, the ability to generate (in some cases, spontaneously) select cytokines. Whether this is attributable to effects on Th1/Th2 levels in the hosts and/or due to potential effects of the EMF on cellular functions remains to be determined.

Single-Nucleotide Polymorphisms in Interleukin 6 (IL-6) Gene Are Associated with Suicide Behavior in an Iranian Population.

Previous association studies have demonstrated the association between immune regulatory genes and suicide behavior. Among these genes are those coding for cytokines. In the present study, we genotyped two interleukin 6 (IL-6) variants (rs2069845 and rs1800795) in 320 suicide attempters, 236 suicide completers, and 341 individuals without any history of psychiatric disorders or suicide ideation. The rs2069845 was not associated with suicide behavior. The rs1800795 C allele was significantly more common among suicide completers compared with suicide attempters (OR (95% CI) = 1.33 (1.04-1.71)), adjusted P = 0.04). Besides, the rs1800795 was associated with the lethality of suicide attempt in recessive model (adjusted P value = 0.01). Consequently, the present study supports the role of IL-6 in suicide behavior and warrants further researches to confirm its effect and explain the underlying mechanism.