IL-10 Genotypes Research Articles

Recipient interleukin 6 gene polymorphism and expression predict HCV recurrence post liver transplantation.

Liver transplantation (LTX)is a lifesaving- effective protocol for patients suffering end stage liver disease (ESLD) and its complications post HCV infection. Recurrence of disease is a frequent clinical complication that is observed in patients undergoing LTX. Cytokines play a central role in the immunological events occurring after the surgery. Using Allelic Discrimination PCR, the allelic variation G174C of IL-6 gene was investigated. The abundance of IL6- mRNA and plasma IL6 cytokine levels were evaluated by using qRT-PCR in peripheral blood mononuclear cells (PBMCs) and enzyme-linked immunosorbent assay (ELISA) respectively in 76 liver transplant recipients recruited from Al Sahel teaching hospital, Ministry of Health and Population Cairo Egypt within the period between June 2015 and October 2017. The frequencies of IL-6 GG genotype and the G allele were significantly detected more in LTX recipients who experienced HCV recurrence versus those who did not suffer recurrence when compared to healthy controls (P=0.001) and (P=0.006), respectively. On the contrary, levels of IL-6 related transcripts in PBMC's of recurrent patients were indifferent from non-recurrent patients and healthy controls (P≥0.124). Interestingly, the circulating IL-6 protein in plasma was significantly elevated in recurrent as compared to the non-recurrent recipients (P=0.002). HCV recurrence post liver transplantation occur more frequently in patients with -174 G/G IL-6 genotype and elevated plasma IL-6 levels.

IL-1β, IL-6, IL-10, and TNFα Single Nucleotide Polymorphisms in Human Influence the Susceptibility to Alzheimer’s Disease Pathology

Neuroinflammation plays an important role in Alzheimer's disease (AD). During this process, activated microglia release pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor α (TNFα) that participate in neuron damage, but also anti-inflammatory cytokines (such as IL-10), which maintain homeostasis of immune response. Previous studies showed the association of IL-1α -889C/T (rs1800587), IL-1β-1473G/C (rs1143623), IL-6 -174C/G (rs1800795), IL-10 -1082G/A (rs1800896), and TNFα -308A/G (rs1800629) polymorphisms with AD. We aimed to investigate whether people with certain IL-1α, IL-1β, IL-6, IL-10, and TNFα genotypes in these polymorphisms are more prone to develop AD-related pathology, reflected by pathological levels of cerebrospinal fluid (CSF) AD biomarkers including amyloid-β1-42, total tau (t-tau), tau phosphorylated at Thr 181 (p-tau181), Ser 199 (p-tau199), and Thr 231 (p-tau231), and visinin-like protein 1 (VILIP-1). The study included 115 AD patients, 53 patients with mild cognitive impairment, and 11 healthy controls. The polymorphisms were determined using real-time polymerase chain reaction. Levels of CSF biomarkers were determined by enzyme-linked immunosorbent assay. A significant increase in p-tau CSF levels was found in patients with the AA IL-10 -1082G/A and GG TNFα -308A/G genotypes, and in carriers of a G allele in IL-1β -1473C/G and IL-6 -174C/G polymorphisms. t-tau levels were increased in carriers of a G allele in IL-1β -1473C/G polymorphism. An increase in VILIP-1 levels was observed in patients with CG and GG IL-1β -1473C/G, GC IL-6 -174C/G, and GG TNFα -308A/G genotype. These results suggest that persons carrying certain genotypes in IL10 (-1082G/A), IL1β (1473C/G), IL6 (-174C/G), and TNFIα (-308A/G) could be more vulnerable to development of neuroinflammation, and consequently of AD.

Interaction Between Dietary Acid Load and IL6 -572 G/C Polymorphism on Blood Pressure Among Postmenopausal Women in Malaysia

Abstract Objectives We examined whether IL6 single nucleotide genetic polymorphism modified the association between dietary acid load (DAL) and blood pressure among postmenopausal women in Malaysia. Methods A total of 211 community-dwelling postmenopausal women were recruited. Dietary intakes of participants were assessed using a validated interview-administered semi-quantitative food frequency questionnaire while DAL was estimated using potential renal acid load (PRAL). Agena® MassARRAY genotyping analysis was used to identify the IL6 genotype and blood pressure was measured using a Digital Automatic BP monitor (OMRON HEM-907, Japan). Interaction between DAL and IL6 -572 G/C polymorphism was assessed using linear regression test. Results There was a significant interaction between DAL and IL6 -572 G/C polymorphism on systolic blood pressure (SBP) (Pinteraction = 0.041). A significant positive association between DAL and SBP with stronger relationship in CG and GG genotype carriers compare to CC carriers were observed. On the other hand, there was no significant diet-gene interaction effect on diastolic blood pressure. Conclusions Our findings suggest that the association between DAL and SBP might be influenced by IL6 -572 G/C polymorphism among postmenopausal women. Further work on how IL6 -572 G/C polymorphism influences the association with DAL on hypertension are warranted. Funding Sources Supported by Fundamental Research Grant Scheme (FRGS), Ministry of Higher Education Malaysia, and Putra Grant UPM.

Analyzing IL6 gene polymorphism in patients with various clinical forms of pulmonary tuberculosis

Throughout the world, tuberculosis still remains one of the most important public health problems. According to numerous publications, TB infectrion is considered as a genetically determined disease, and host genetical polymorphism underlies a mechanism resulting in disease progression from primary infection to clinical manifestations. Currently, an association between TB infection and IL6 gene polymorphism at position -174 responsible for low cytokine production has been extensively investigated. Previously, we evaluated the association between IL6 gene alleles and genotypes and predisposition/resistance to tuberculosis in Russian descendants residing in the Chelyabinsk Region. Here, we conducted a comparative analysis for prevalence of IL6 gene alleles and genotypes in patients differed in lung damage degree such as infiltrative, focal, and fibrous-cavernous forms of pulmonary tuberculosis by isolating whole blood DNA samples and subsequent genotyping of IL6 gene polymorphisms with polymerase chain reaction and agarose gel electrophoresis. We found that patients with a focal TB form were characterized by prevalence of IL6(-174)*C/C genotype associated with low cytokine production, whereas patients with severe fibrous-cavernous carried IL6(-174)*G/C genotype accounting for modedrated IL-6 production.

The polymorphisms of IL-6/STAT3 signaling pathway may contribute to cutaneous T-cell lymphomas susceptibility

IL-6/STAT3 signaling pathway has been suggested to play a role in CTCL pathogenesis. Polymorphisms in STAT3 signaling pathway-related genes might be a risk factor for CTCL. However, the exact role of inherited gene polymorphisms of IL-6 and STAT3 in the pathogenesis of CTCL is still not fully understood. The aim was to examine whether IL-6 cytokine and polymorphisms of IL-6 and STAT3 gene are associated with CTCL susceptibility, stage of disease and pruritus intensity. We compared the IL-6 serum level and the frequency of selected single nucleotide polymorphisms of IL-6 and STAT3 in 106 CTCL and 198 control group using polymerase chain reaction with sequence-specific primers method and ELISA. We have found that serum IL-6 level in CTCL patients was significantly higher than in healthy controls (p < 0.05). We also demonstrated that two genotypes, CC of IL-6 and GG of STAT3, were overexpressed in CTCL patients compared to healthy controls, and that they increase the risk of malignancy development (OR = 1.8, p = 0.04 for IL-6 and OR 2.53, p = 0.0064 for STAT3). Moreover, the GG genotype of STAT3 polymorphism seems to be associated with lack of pruritus or mild pruritus in CTCL patients. Our results indicate that IL-6 is involved in pathogenesis of CTCL but not pruritus. Moreover, CC of IL-6 and GG genotype of STAT3 genes might be considered as the risk factor for development of CTCL.

Relationships Between IL-13 and IL-4 Genotypes and Aeroallergens with Risk of Allergic Rhinitis in Iranian-Azeri.

Background: Up to 40% of the world populations are affected by allergic rhinitis (AR). Interplay between genetics, epigenetics, and environmental factors leads to allergic disease. Objective: In this study, we evaluated the accompaniment between polymorphic variants of IL-13 and IL-4 and aeroallergens among Iranian-Azeri children and adolescent in AR's risk. Methods: Five-hundred AR patients and 300 healthy individuals were enrolled in this study after diagnosis via blood testing for IgE and skin prick test by subspecialty of Allergy and Immunology from Azerbaijan, northwest of Iran, from 2017 to 2019. Genomic DNA was prepared from all samples for genotyping of IL-4 and IL-13. Results: We identified genetic variation of IL-13 and IL-4 and important aeroallergens that could increase the AR risk during childhood and adolescent. The risk of AR increased in the subjects with +2044GA genotype of IL13 [adjusted odds ratio (OR), 1.80; 95% confidence interval (CI), 0.97-3.33] and -590CT genotype of IL4 (adjusted OR, 1.94; 95% CI, 1.00-3.87) in childhoods, compared with the control subjects. However, none of genotypes and allele frequencies of IL4 -590C/T and IL13 +2044G/A polymorphisms revealed significant variation between the AR patients and controls in adulthood. The frequency of sensitization to pollens was high in all genotypes of IL4 -590C/T and IL13 +2044G/A polymorphisms in both age groups of AR patients. Conclusion: AR is considered to be the most common form of atopic disease. Susceptible individuals had family history of allergic disease and indicated sensitivity to various environmental factors. In this study, pollen and feather played an important role in occurrence of AR. Childhood with GA at IL13 +2044 and CT at IL4 -590 are at increased risk for AR. Moreover, further studies with more samples are required to confirm our findings and also to help us develop new procedure for genetically detecting more efficient proceedings of prevention and intervention.

The role of IL‐6 in immunotherapy of non‐small cell lung cancer (NSCLC) with immune‐related adverse events (irAEs)

IL‐6 is a cytokine that plays an important role in response to injury or infection and is a promising biomarker for predicting poor prognosis and therapeutic targets in non‐small cell lung cancer (NSCLC). This article reviews the biochemical mechanism, function and genotype of IL‐6, and summarizes the diagnostic and prognostic value of IL‐6 level. Anti‐IL‐6 therapy does not affect the effect of immunocheckpoint inhibitors (ICIs), but enhances its anticancer function, which may be the treatment option for immune‐related adverse events (irAEs) in the future. Therefore, IL‐6 may be a therapeutic target for the treatment of NSCLC.

Cytokine gene polymorphisms in Pigeon Breeder's Disease expression.

Background:Exaggerated immunological response to repeated inhalation of organic or chemical dusts may lead to Hypersensitivity Pneumonitis among sensitized individuals. Only a few exposed individuals became ill and disease expression pattern is highly variable which suggest that genetic factors may play a role.Aim:To investigate interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-ß, and IL-10 gene polymorphisms in a cohort of pigeon breeder’s disease (PBD) patients in comparison with exposed but healthy controls and the association with different patterns of disease.Methods:We evaluated 40 PBD patients and 70 exposed controls. IFN-γ, TNF-α, IL-6, TGF-ß, and IL-10 polymorphisms were determined by polymerase chain reaction–sequence specific primer amplification.Results:Polymorphism analysis of IFN-γ, TNF-α, IL-6, TGF-ß, and IL-10 genotypes and allele frequencies showed no differences between patients and controls. IFN-γ T/T genotype frequency was increased among patients with chronic presentation (RR=2.33, p=0.047) compared with those with acute/subacute presentation. Also, chronic presenting patients had an increased frequency of IFN-γ T allele (50% vs 22.5%, RR=1.76, p=0.011). No differences were found in TNF-α, IL-6, TGF-ß, and IL-10 genotypes neither allelic frequencies between both groups of patients. IL-6 C/C genotype was more frequent in patients who showed chronic evolution (RR=2.54, p=0.017), when comparing with patients with disease resolution.Conclusion:IFN-γ T/T and the IL-6 C/C genotypes seem to play a role in HP expression due to avian exposure, as their frequencies are increased in chronic presentations or in those with chronic evolution one year after the initial diagnosis, respectively. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (3): e2020004)

Association of IL-6 -174G > C and -572G > C Polymorphisms with Risk of Legg-Calve-Perthes Disease in Iranian Children

Background Legg-Calve-Perthes disease (LCPD) is an idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head with multifactorial etiology. The aim of this study was to analyze the association of IL-6 polymorphisms with LCPD risk in Iranian children. Methods: The study comprised of 45 children diagnosed with LCPD and 60 healthy subjects. The IL-6 -174 G > C and -597 G > C polymorphisms were genotyped by PCR-RFLP assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated on the risk genotypes and alleles. Results: The mutant homozygote genotype (CC) of IL-6 -174 G > C polymorphism was associated with increased risk of LCPD (OR 3.554; 95% CI: 0.1.578–8.004; p = 0.002). There was no significant association between IL-6 -597 G > C polymorphism and an increased risk of LCPD. Conclusions: Our results suggest that the IL-6 -174 G > C but not the IL-6 -597 G > C polymorphism may increase LCPD susceptibility in Iranian children.

Interactions Between Diet Quality and Interleukin-6 Genotypes Are Associated With Metabolic and Renal Function Parameters in Mexican Patients With Type 2 Diabetes Mellitus

The aim of this study was to evaluate the interaction between diet quality and interleukin (IL)-6 genotypes and its association with metabolic and renal function parameters in Mexican patients with type 2 diabetes mellitus (T2DM). Using an analytical cross-sectional design, 219 patients with T2DM (92 men; age 62±10years) were evaluated for selected metabolic and renal function parameters. Diet quality according to the Healthy Eating Index was evaluated and classified as good diet or poor diet in all patients. IL-6 serum concentrations and genotypes and haplotypes for IL6-597G>A (rs180097), -572G>C (rs180096), and -174G>C (rs180095) polymorphisms were determined. Eighty-two percent of patients reported having a poor diet. Carriers of alleles -572C and -174C showed higher high-density lipoprotein cholesterol levels (44±12 vs. 40±9mg/dL; P = .01) and lower total cholesterol levels (184±33 vs. 197±42mg/dL; P=.03) than did those homozygous for G/G. Neither IL6 genotypes nor haplotypes were significantly associated with serum concentrations of IL-6. Some significant interactions between IL6 genotypes/haplotypes and diet quality were associated with body mass index, waist circumference, high-density lipoprotein cholesterol levels, and estimated glomerular filtration rate. Interactions between diet quality and IL6 genotypes/haplotypes were associated with the main metabolic and renal function parameters in Mexican patients with T2DM. It will be important to consider genetic profiles in designing dietary portfolios and nutritional interventions for the management of such patients.

Identification of Periopathogenes from Dental Plaque in Periodontal Patients with PCR Technique and Their Association with Composite Interleukin-1 Genotype.

The present study aimed to assess the presence of main types of microorganisms involved in the aetiopathogenesis of chronic periodontitis with PCR technique and determinates the presence of composite IL-1 genotype and their associations with founded bacteria. The examined group was consisted from 20 subjects with diagnosed chronic periodontitis and 20 healthy control without periodontitis. Clinical parameters like gingival index (GI), plaque index (PI), bleeding on probing (BOP), periodontal pocket depth (PPD) and clinical attachment lost (CAL) were determinates. Subgingival dental plaque was collected using a sterilized paper point. We used Parodontose Plus test, reverse hybridization kit, for the detection of periodontal marker bacteria, as well as for the detection of composite Interleukin -1 Genotype Results: The most present bacterial species detected from subgingival dental plaque was Treponema denticola and Porfiromonas gingivalis which was present in 65% of examined patients. In relation to the presence of positive genotype in patients, there was no significant difference between the test and control group for p> 0.05 (p = 1.00). For χ2=8,17 (p=0,06, p<0,05) there is an association between Prevotella intermedia, and composite genotype. Between positive genotype and analyzed bacterial species A. actinomycetem comitans for p> 0.05 (p = 1.00), P. gingivalis for p> 0.05 (p = 0.16), T. Forsythia for p> 0.05 (p = 0.20), T. Denticola for p> 0.05 (p = 0.64) no association was found. This investigations confirmed the strong association of these five examined periopathogenes with periodontitis.

Validation study of the association between genetic variant of IL4 and severe radiation pneumonitis in lung cancer patients treated with radiation therapy

Background and purposeRecent researches demonstrated that single nucleotide polymorphisms (SNPs) of genes involving inflammation, DNA repair, etc. were associated with risk of radiation pneumonitis (RP). However, these studies were single-centered, from single ethnic origin, without validation from independent cohort studies from other populations. In order to identify clinical valuable SNPs for RP, in this study we selected 19 RP-related SNPs candidates previously published before 2016 for validation in our cohort. Material and methods359 lung cancer patients with radiotherapy were included in our prospective study (NCT02490319). Peripheral blood samples from these patients were genotyped by MassArray and Sanger Sequence method. Multivariate Cox hazard and other analyses were applied to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of all factors possibly related to the risk of RP. ResultsPatients with elder age, MLD ≥15 Gy, V20 ≥24% had higher risk of RP ≥grade 3 compared with their counterparts (HR = 2.020, 95% CI: 1.045–3.906, P = 0.037; HR = 2.502, 95% CI: 1.346–4.652, P = 0.004; HR = 2.256, 95% CI: 1.191–4.272, P = 0.013, respectively). Moreover, patients receiving IMRT were associated with decreased incidence of RP (HR = 0.520, 95% CI: 0.280–0.963, P = 0.037). Importantly, CT + TT genotype of IL4: rs2243250 was strongly related to decreased risk of RP ≥grade 3 (HR = 0.195, 95% CI: 0.090–0.424, P = 0.000037, Pc = 0.0006). ConclusionIL4: rs2243250 was validated to be significantly related to RP of grade ≥3 in our cohort. Our results further emphasized the prevalence and clinical value of IL4: rs2243250 on RP, and may thus be one of the important predictors of severe RP before radiotherapy.

Association between interleukin-10 genetic variant (-1082G>A) with detection and severity of respiratory distress syndrome in preterm neonates.

Abnormal cytokine production derived from specific polymorphisms can have effect on development of respiratory distress syndrome (RDS). Therefore, the present study aimed to determine whether polymorphisms of IL10 in preterm newborn are associated with RDS. A total of one hundred and one venous blood samples were collected from preterm neonates, and they were classified as 51 with no RDS and 50 with RDS. Grading of RDS, history of surfactant administration or ventilator was assessed in the diseased group. Genetic variant of IL10-1082G/A (rs1800896) was genotyped by PCR-RFLP. The RDS group showed a higher prevalence of IL10-1082 AA and lower prevalence of IL10-1082 GG (p<.001). We found that the incidence of the allele G in the IL10-1082 polymorphism was lower in the RDS group (24%) than the non-RDS group (51%) (p<.001). Allele model (A vs. G): OR=0.304, 95% CI: 0.166-0.554, p≤.001; Dominant model (AA vs. AG+GG): OR=0 0.470, 95% CI: 0.282-0.783, p=.04. More severe grades of RDS, need for surfactant and mechanical ventilation, were significantly associated with AA genotype when compared to AG+GG genotypes. IL10 (AG+GG) genotypes were considered as an independent predictor for lower risk of RDS within preterm neonates. IL10-1082 A/A genotype associated with increased susceptibility to RDS. Also, A allele has been associated with increase severity of RDS in preterm neonates. Regression analysis revealed that IL10 AG+GG genotypes were considered as independent predictors for lower risk development of RDS within preterm neonates.

496 STAT3 polymorphisms and IL-6 polymorphism are associated with the risk of basal cell carcinoma in patients from northern Poland

Basal cell carcinoma (BCC) environment consists of stromal and inflammatory cells which produce variety of cytokines, chemokines and growth factors that may affect the tumor behavior. One of the cytokines suggested to be involved in the pathogenesis of BCC is IL-6 - the upstream element of IL-6/JAK/STAT3 pathway. In the present study rs1800795 (-174 G/C) IL-6 gene polymorphism and STAT3 rs2293152 (intron 11, C/G) and rs4796793 (–1697, C/G) polymorphisms were assessed in relation to the BCC risk and clinical course. Additionally, IL-6 serum level was assessed in relation to IL-6 genotype and clinical variables. The study included 254 unrelated BCC patients (mean age 70.39±11.43) and 198 healthy, unrelated age- and sex-matched volunteers. We have found that the presence of C allele in rs1800795 IL-6 gene polymorphism was associated with increased risk of BCC (aOR: 1.86; 95% CI=1.22-2.84; p=0.004). The presence of CC genotype in STAT3 rs2293152 polymorphism was associated with increased BCC risk in recessive model analysis (aOR=3.94; 95% CI: 1.59-9.77; p=0.003). In contrast, the presence of GC genotype in overdominant model was associated with decreased risk of BCC (aOR=0.24; 95% CI:0.12-0.49; p<0.0001). The presence of C allele in STAT3 rs2293152 polymorphism was associated with increased risk of BCC (aOR: 1.31; 95% CI:1.01-1.69; p=0.04). The presence of GG genotype in STAT3 rs4796793 polymorphism was associated with increased BCC risk in recessive model analysis (aOR=3.66; 95% CI:1.33-10.10; p=0.012). The presence of G allele in STAT3 rs4796793 polymorphism was associated with increased risk of BCC (aOR: 1.59; 95% CI: 1.01-2.49; p=0.04). IL-6 serum level positively correlated with the tumor size.

STAT3 polymorphisms and IL-6 polymorphism are associated with the risk of basal cell carcinoma in patients from northern Poland

Basal cell carcinoma (BCC) environment consists of stromal and inflammatory cells which produce variety of cytokines, chemokines and growth factors that may affect tumor behavior. One of the cytokines suggested to be involved in the pathogenesis of BCC is IL-6, which is the upstream element of IL-6/JAK/STAT3 pathway. The correlation between polymorphisms of the genes related to this pathway and cancer risk/prognosis have been previously investigated in several neoplasia, but available data concerning BCC are scarce. In the present study, rs1800795 (-174 G/C) IL-6 gene polymorphism and two polymorphisms in the STAT3 gene, namely rs2293152 (intron 11, C/G) and rs4796793 (-1697, C/G) were assessed in relation to the BCC risk and clinical course. Additionally, IL-6 serum level was assessed in relation to IL-6 genotype and clinical variables. The study included 254 unrelated patients with BCC and of mean age 70.39 ± 11.43 (69.83 ± 12.32 women, 71.03 ± 10.31 men) and 198 healthy, unrelated age- and sex-matched volunteers. IL-6 and STAT3 polymorphisms were analyzed using polymerase chain reaction with sequence-specific primers (SSP-PCR). Serum concentration of IL-6 was measured using the ELISA test. We have found that the presence of C allele in rs1800795 IL-6 gene polymorphism was associated with increased risk of BCC (aOR 1.86; 95% CI 1.22–2.84; p = 0.004). The presence of CC genotype in STAT3 rs2293152 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.94; 95% CI 1.59–9.77; p = 0.003). In contrast, the presence of GC genotype in overdominant model was associated with decreased risk of BCC (aOR = 0.24; 95% CI 0.12–0.49; p < 0.0001). The presence of C allele in STAT3 rs2293152 polymorphism was associated with increased risk of BCC (aOR 1.31; 95% CI 1.01–1.69; p = 0.04). The presence of GG genotype in STAT3 rs4796793 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.66; 95% CI 1.33–10.10; p = 0.012). The presence of G allele in STAT3 rs4796793 polymorphism was associated with increased risk of BCC (aOR 1.59; 95% CI 1.01–2.49; p = 0.04). IL-6 serum level positively correlated with the tumor size.

Inflammation-related genes are associated with epigenetic aging in HIV.

Chronic inflammation is characteristic of both HIV and aging ("inflammaging") and may contribute to the accelerated aging observed in people living with HIV (PLWH). We examined whether three inflammation-related single-nucleotide polymorphisms (SNPs) were risk factors for accelerated aging and HIV-associated, non-AIDS (HANA) conditions among PLWH. We examined 155 postmortem cases with HIV (mean age = 47.3, 81% male, 68% self-reported White) from the National NeuroAIDS Tissue Consortium who had pre-mortem neurobehavioral/medical/virologic data and epigenomic data from occipital cortex tissue. Accelerated aging was measured according to the Epigenetic Clock; an aging biomarker based on DNA methylation levels. Past or current age-associated HANA conditions including cerebrovascular, liver and kidney disease, chronic obstructive pulmonary disease, cancer, and diabetes were determined via self-report. Epigenetic Aging Z-scores and likelihood of past/current HANA conditions were compared between major allele homozygotes and minor allele carriers for each SNP (IL-6 - 174G>C, IL-10 - 592C>A, TNF-α - 308 G>A) separately. Analyses were adjusted for relevant demographic/clinical factors. Epigenetic aging (e.g., higher Z-scores) was significantly greater in IL-6 C allele carriers (p = .002) and IL-10 CC homozygotes (p = .02) compared to other genotype groups. The likelihood of any past/current HANA condition did not differ by IL-10 genotype but was 3.36 times greater in IL-6 C allele carriers versus others (OR = 3.36, 95%CI = 1.09-10.34, p = .03). TNF-α genotype was not associated with epigenetic aging or HANA conditions. IL-6 and IL-10 SNPs may help to identify PLWH who are at high risk for accelerated aging. These insights into pathophysiological pathways may inform interventional approaches to treat rapid aging among PLWH.

Altered levels of placental miR-338-3p and miR-518b are associated with acute chorioamnionitis and IL6 genotype

Placental-derived miRNAs are attractive candidates as biomarkers of placental health, but their associations with specific pathologies, such as acute chorioamnionitis (aCA), are not well explored. Samples of chorionic villi from 57 placentas (33 aCA and 24 non-aCA) were analyzed. Expression was quantified for six candidate miRNAs (miR-146a, miR-210, miR-223, miR-338-3p, miR-411, and miR-518b), using quantitative real-time PCR. miR-518b and miR-338-3p were differentially expressed between aCA cases and non-aCA cases (Bonferroni-corrected p < 0.05). Further, we observed that placental miR-518b expression was associated with an IL6 SNP (rs1800796), a polymorphism we previously reported as a risk-conferring variant for aCA.

Association of polymorphisms at −174 in IL-6, and −308 and −238 in TNF-α, in the development of tuberculosis and type 2 diabetes mellitus in the Mexican population

Polymorphisms at −176 in IL-6, and −238 and −308 in TNF-α have been described as risk factors for developing tuberculosis (TB) and type 2 diabetes mellitus (T2DM). However, it is not known how these changes influence the development of TB-T2DM comorbidity. The objective of this work was therefore to analyze the impact of these polymorphisms in the Mexican population.This is a cross-sectional study of cases and controls in which polymorphisms at −174 in IL-6, −238 and −308 in TNF-α were identified in healthy subjects, those with TB, T2DM and carriers of the comorbidity, each group consisted of 30 individuals. Descriptions of the population, frequency of genotypes and risk association were calculated, and a reduction of multifactorial dimensionality between groups (MDR) was determined.Genotype 174 G/G-of IL-6 was observed in 78% of individuals, while −308 G/G and −238 G/G of TNF-α occurred in 90% and 91% of individuals, respectively. The −174 G/G IL-6 in individuals with T2DM increased five-fold (p = .02) the risk of developing the comorbidity. The MDR analysis showed that the association of −174 G/G IL-6 and −308 G/G TNF-α in healthy individuals increased the risk of developing the comorbidity up to six-fold (p = .019), while in individuals with T2DM, this risk augmented 14-fold (p = .0002).The −174 G/G IL-6 genotype increases the risk of developing comorbidity in the T2DM population and this risk is raised when associated with −308 G/G TNF-α. These findings have implications for understanding the epidemiological dynamics of the TB-T2DM comorbidity, promoting prevention strategies and inhibiting the development of this co-morbidity.

Association of a PD-L2 Gene Polymorphism with Chronic Lymphatic Filariasis in a South Indian Cohort.

Lymphatic filariasis (LF) is a parasitic infection, caused by three closely related nematodes, namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. Previously, we have shown that lysate from B. malayi microfilariae induces the expression of interleukin (IL)-10 and programmed death-ligand (PD-L) 1 on monocytes, which lead to inhibition of CD4+ T-cell responses. In this study, we investigated associations of IL-10 and programmed cell death (PD)-1 pathway gene polymorphisms with clinical manifestation in LF. We evaluated the frequency of alleles and genotypes of IL-10 (rs3024496, rs1800872), IL-10RA (rs3135932), IL-10RB (rs2834167), PD-1 (rs2227982, rs10204525), PD-L1 (rs4143815), PD-L2 (rs7854413), and single-nucleotide polymorphisms (SNPs) in 103 patients with chronic pathology (CP), such as elephantiasis or hydrocele and 106 endemic normal (EN) individuals from a South Indian population living in an area endemic for LF. Deviations from the Hardy-Weinberg equilibrium were tested, and we found a significant difference between the frequency of polymorphisms in PD-L2 (rs7854413; P < 0.001) and IL-10RB (rs2834167; P = 0.012) between the CP and the EN group, whereas there were no significant differences found among IL-10, IL-10RA, PD-1, and PD-L1 SNPs. A multivariate analysis showed that the existence of a CC genotype in PD-L2 SNP rs7854413 is associated with a higher risk of developing CP (OR: 2.942; 95% confidence interval [CI]: 0.957-9.046; P = 0.06). Altogether, these data indicate that a genetically determined individual difference in a non-synonymous missense SNP of PD-L2 might influence the susceptibility to CP.

Influence of genetic variants of gamma interferon, interleukins 10 and 12 on Visceral Leishmaniasis in an endemic area, Iran

ABSTRACTVisceral leishmaniasis (VL) is a life threatening disease in which a variety of cytokines regulating the immune responses can determine its outcome. As based on their region in the gene, some single nucleotide polymorphisms (SNP) can influence the expression of their corresponding proteins, this study aimed to investigate the association between SNP in the IL-10, IL-12, IFN-γ genes and susceptibility to VL. The study was carried out on 120 patients with VL, 67 patients’ families (family group), and 102 healthy individuals with positive leishmanin skin test as positive control group. SNPs in IL-10 (−592, −819, −1082), IL-12 (+1188) were analyzed using PCR-RFLP and allele specific polymerase chain reaction (ASPCR) was used to analyze SNPs in IFN-γ (+874 A/T). The results showed that at position +874 of IFN-γ, AT genotype was significantly more frequent in patients than that in families and controls, but TT genotype was significantly more frequent in families than in patients. Distributions of IFN-γ alleles were not significantly different between the study groups. As for IL-12 and IL-10 genotypes and alleles, no significant difference was observed between the groups. Although a strong linkage disequilibrium was observed between alleles −592, −819 and −1082 of IL-10, distributions of the most common haplotypes and haplogenotypes reconstructed from IL-10 alleles were not significantly different between the study groups.It could be suggested that heritage of AT genotype at position +874 of IFN-γ may predispose and TT genotype can resist individual to VL in an endemic area in the southwest of Iran.