Gene Polymorphisms of Patients with Lymphoma-Associated Hemophagocytic Syndrome in Longyan area, Fujian Province / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene polymorphisms of patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province.@*METHODS@#A total of 125 patients with lymphoma-associated hemophagocytic syndrome in Longyan, Fujian province, admitted to Longyan First Hospital from May 2017 to November 2020 were selected. Peripheral venous blood was collected from all the patients, and the genotypes of perforin 1 (PRF1) and interleukin-10 (IL-10) gene loci were detected by PCR-fluorescence probe method, and the correlation between PRF1 and IL-10 gene polymorphisms and lymphoma-associated hemophagocytic syndrome was analyzed.@*RESULTS@#The mutation frequencies of PRF1 gene loci rs885821 (C>T), rs885822 (C>T), rs1889490 (G>A) in patients with lymphoma-associated hemophagocytic syndrome were 10.40%, 78.8% and 64.4%, respectively. The mutation frequencies of rs1800872 (A>C), rs1800871 (C>T) and rs1800896 (G>A) of IL-10 loci were 56.0%, 45.2% and 77.6%, respectively.@*CONCLUSION@#PRF1 and IL-10 gene loci were polymorphic in patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. Alleles C and G of PRF1 and IL-10 were risk factors, and alleles T and A were protective factors.

AF4/FMR2 and IL-10 gene single nucleotide polymorphisms are correlated with disease susceptibility and immune infiltration in ankylosing spondylitis / 南方医科大学学报

OBJECTIVE@#To explore the correlation of polymorphisms of AF4/FMR2 family genes and IL-10 gene with genetic susceptibility to ankylosing spondylitis (AS) and identify the high-risk factors of AS.@*METHODS@#This case-control study was conducted among 207 AS patients and 321 healthy individuals. The tag single nucleotide polymorphisms (SNPs) rs340630, rs241084, rs10865035, rs1698105, and rs1800896 of the AF4/FMR2 family gene and IL-10 gene of the AS patients were genotyped, and the distribution frequencies of the genotypes and alleles were analyzed to explore the relationship between different genetic models and AS and the gene-gene and gene-environment interactions.@*RESULTS@#Gender ratio, smoking history, drinking history, hypertension, erythrocyte sedimentation rate and C-reactive protein differed significantly between the case group and the control group (P < 0.05). The dominant model and recessive model of AFF1 rs340630, the recessive model of AFF3 rs10865035, and the recessive model of IL-10 rs1800896 were significantly different between the two groups (P=0.031, 0.010, 0.031, and 0.019, respectively). Gene-environment interaction analysis suggested that the interaction model incorporating AFF1 rs340630, AFF2 rs241084, AFF3 rs10865035, AFF4 rs1698105, IL-10 rs1800896, smoking history and drinking history was the best model. The genes related with AF4/FMR2 and IL-10 were enriched in the biological processes of AF4 super extension complex, interleukin family signal transduction, cytokine stimulation and apoptosis. The expression levels of AF4/FMR2 and IL-10 were positively correlated with immune infiltration (r > 0).@*CONCLUSION@#The SNPs of AF4/FMR2 and IL-10 genes are associated with the susceptibility to AS, and the interactions of AF4/FMR2 and IL-10 genes with the environmental factors contributes causes AS through immune infiltration.

Formononetin enhances the antitumor effect of H22 hepatoma transplanted mice / 细胞与分子免疫学杂志

Objective To explore the effect of formononetin on immunity of mice with transplanted H22 hepatocarcinoma. Methods Male C57BL/6 mice were subcutaneously inoculated with H22 cells (4×105) to establish a tumor-bearing mouse model. The mice were treated with formononetin [10 mg/(kg.d)] or [50 mg/(kg.d)] for 28 days, and then the tumor inhibition rate was calculated. Carrilizumab was used as a positive control drug. The expressions of CD8, granzyme B and forkbox transcription factor 3 (FOXP3) in HCC tissues were analyzed by immunohistochemical staining. The mRNA and protein expression of programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) in HCC tissues were detected by real-time PCR or Western blot analysis, respectively. The serum levels of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were detected by ELISA. Results Formononetin increased the tumor inhibition rate and the positive rate of CD8 and granzyme B staining in tumor-bearing mice. There was no significant difference in the positive rate of FOXP3 staining in tumor tissues of mice in each group. Formononetin decreased the levels of IL-10 and TGF-β in serum of tumor-bearing mice, and decreased the relative expression of mRNA and protein of PD-1 and PD-L1 in tumor tissue of tumor-bearing mice. Conclusion Formononetin can activate CD8+ T cells and reduce the release of immunosuppressive factors in regulatory T cells by blocking PD-1/PD-L1 pathway and play an antitumor role.

Effects of Huangqin Tang on NLRP3/Caspase-1 pathway in mice model of ulcerative colitis / 中国中药杂志

The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1β, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1β, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1β, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1β, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.

Effect of moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4) on immune function in healthy rats based on intestinal flora / 中国针灸

OBJECTIVE@#To observe the effects of moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4) on immune function and intestinal flora in healthy rats, thereby investigating the underlying mechanism of moxibustion on immune function.@*METHODS@#Twenty 8-week-old SD rats were randomly divided into a young blank group and a young moxibustion group, with 10 rats in each group. Similarly, twenty 8-month-old SD rats were randomly divided into a middle-aged blank group and a middle-aged moxibustion group, with 10 rats in each group. The rats in the two moxibustion groups received moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4), 15 min per session, once daily, five times a week, for a total of four months. The rats in the two blank groups were fed under normal conditions. After the intervention, thymus and spleen indexes were calculated; the morphology of thymus and spleen tissues was observed using HE staining; the flow cytometry was used to detect the expression of CD and CD T lymphocytes and the CD/CD ratio was calculated; ELISA was used to measure the serum levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-17 (IL-17); 16S rRNA high-throughput sequencing was used to analyze the intestinal flora. Additionally, the correlation between the relative abundance of intestinal flora and serum levels of TNF-α, IFN-γ, IL-6, IL-10 and IL-17 was analyzed.@*RESULTS@#Compared with the young blank group, the young moxibustion group exhibited an increase in the cortical area of thymus tissue with tighter lymphocyte arrangement; compared with the middle-aged blank group, the middle-aged moxibustion group showed an increase in thymus index (P<0.05) and an increase in the cortical area of thymus tissue. There were no significant differences in spleen index between the 2 moxibustion groups and the 2 blank groups (P>0.05). There were no significant differences in the expression of CD, CD, and CD/CD ratio between the 2 moxibustion groups and the corresponding blank groups (P>0.05). Compared with the young blank group, the young moxibustion group had elevated IL-6 level (P<0.05); compared with the middle-aged blank group, the middle-aged moxibustion group had decreased IL-10 and IL-17 levels (P<0.05). Compared with the young blank group, the young moxibustion group exhibited increased Sobs index, Ace index, and Chao index (P<0.01, P<0.05), as well as increased relative abundance of Spirochaetota, Treponema, Turicibacter, Rikenellaceae_RC9_gut_group (P<0.05), and decreased relative abundance of Dubosiella (P<0.05). Compared with the middle-aged blank group, the middle-aged moxibustion group had increased relative abundance of Spirochaetota, Treponema, norank_f_Peptococcaceae (P<0.05), and decreased relative abundance of Proteobacteria, Allobaculum, and Faecalibaculum (P<0.05). Correlation analysis revealed that relative abundance of Eubacterium_xylanophilum_group and unclassified _f_Lachnospiraceae was negatively correlated with serum TNF-α level (r=-0.39, P=0.03; r=-0.24, P=0.04), while relative abundance of norank_f_norank_o_Clostridia_UCG-014 and Lactobacillus was positively correlated with serum TNF-α level (r=0.37, P=0.04; r=0.43, P=0.02). The relative abundance of Roseburia and Monoglobus was negatively correlated with serum IFN-γ level (r=-0.40, P=0.02; r=-0.44, P=0.01), while relative abundance of Lactobacillus was positively correlated with serum IL-10 level (r=0.43, P=0.02).@*CONCLUSION@#Moxibustion could improve immune function in healthy rats, and its mechanism may be related to the regulation of relative abundance of intestinal flora.

Effect of different suspension moxibustion methods on syndrome characteristics of rats with rheumatoid arthritis of heat bi syndrome based on "moxibustion can be used for heat syndrome" / 中国针灸

OBJECTIVE@#To observe the effects of different suspension moxibustion methods on the syndrome characteristics and inflammatory factors of rats with rheumatoid arthritis (RA) of heat bi syndrome and to prove the concept of "moxibustion can be used for heat syndrome".@*METHODS@#Among seventy Wistar rats, 12 rats were randomly selected as a normal group, and the remaining rats were induced by collagen combined with wind, dampness, and heat environmental stimulation to establish the RA model of heat bi syndrome. Forty-eight rats with successful model establishment were further randomly divided into a model group and three moxibustion groups (mild moxibustion group, rotating moxibustion group and sparrow-pecking moxibustion group), with 12 rats in each group. The acupoints "Quchi" (LI 11), "Dazhui" (GV 14) and ashi point were used in all moxibustion groups, with mild moxibustion, rotating moxibustion, and sparrow-pecking moxibustion intervention given respectively, each acupoint was treated with moxibustion for 10 min a day, and 6 days were considered one course of treatment, with a total of three courses. After the intervention, the arthritis index (AI), the Evans blue (EB) extravasated volume in the soft tissue of the right hind paw, and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in the serum were measured by ELISA in each group. The volume of the bilateral hind paw was measured; the infrared thermal imaging was collected to analyze the temperature of the plantar area of the bilateral foot pads, and the reaction time of plantar heat pain was calculated before and after modeling, as well as after the 1st, 2nd and 3rd courses of interrention. The ankle dorsiflexion angle of the right hind foot was also measured before and after modeling, as well as after the intervention.@*RESULTS@#After modeling, compared with the normal group, the rats in the model group had more high-temperature areas in the bilateral hind limbs, abnormal AI score, abnormal bilateral hind paw volume, abnormal temperature of the plantar area of the bilateral foot pads, abnormal foot pain response time, abnormal right hind ankle dorsiflexion angle, abnormal right hind paw soft tissue EB extravasation, and abnormal serum TNF-α and IL-10 levels (P<0.01, P<0.05). After the intervention, compared with the model group, the rats in each moxibustion group had decreased or disappeared high-temperature areas in the bilateral hind limbs, EB extravasated volume in the soft tissue of the right hind paw was reduced (P<0.05), and the right ankle dorsiflexion angle was increased (P<0.05), serum level of TNF-α was reduced, and level of IL-10 increased (P<0.05); the AI scores in the mild moxibustion group and the sparrow-pecking moxibustion group was decreased (P<0.01, P<0.05). After the 1st, 2nd and 3rd courses of intervention, compared with the model group, the bilateral hind paw volume of rats in each moxibustion group was decreased (P<0.05, P<0.01), and plantar heat pain reaction time was increased (P<0.05). After the 2nd course and the 3rd course of intervention, the temperature of the right hind paw pad area was decreased in each moribustion group (P<0.05); after the 3rd courses of intervention, the temperature of the left hind paw pad area was decreased in the mild moxibustion group (P<0.05).@*CONCLUSION@#Suspension moxibustion could adjust the serum levels of TNF-α and IL-10 to improve the syndrome characteristics of RA rats of heat bi syndrome, such as joint redness, swelling, heat, pain and activity restriction. The effect of mild moxibustion is the most prominent. The findings could provide scientific basis for "moxibustion can be used for heat syndrome".

Association between interleukin-10 polymorphisms and CD4+CD25+FOXP3+ T cells in asthmatic children

Abstract Objective: The aim of this study was to evaluate the association between possible functional interleukin-10 (IL-10) polymorphisms, IL-10 expression and regulatory T cells (Tregs) frequency, and/or asthma severity in a sample of children and adolescents. Methods: This is a nested case-control genetic association study. The study sample consisted of children and adolescents aged 8-14 from public schools. Four polymorphisms of the IL-10 gene (rs1518111, rs3024490, rs3024496, rs3024491) were genotyped in asthmatic subjects and controls using real-time PCR. Tregs cells and IL-10 were analyzed in peripheral blood mononuclear cells by flow cytometry. The severity of asthma was defined according to the Global Initiative for Asthma (GINA) guideline. Results: One hundred twenty-three asthmatic subjects and fifty-eight controls participated in the study. The single nucleotide polymorphism (SNP) rs3024491 (T allele) showed association with asthma severity, presenting a higher frequency in patients in the moderate asthma group. The T allele of variant rs3024491 also showed an association with reduced IL-10 levels (p = 0.01) and with increased Tregs frequency (p = 0.01). The other variants did not present consistent associations. Conclusions: Our results suggest that moderate asthma is associated with a higher frequency of the T allele in the SNP rs3024491. In addition, the variant rs3024491 (TT) was associated with a reduction in IL-10 production and an increased percentage of Tregs cells, suggesting possible mechanisms that influence asthma severity.

Associations of il-6 -174g>c and il-10 -1082a>g polymorphisms with susceptibility to celiac disease: evidence from a meta-analysis and literature review / Associações de polimorfismos IL-6 -174G> C e IL-10 -1082A>G com suscetibilidade à doença celíaca: evidências de uma meta-análise e revisão de literatura

ABSTRACT BACKGROUND: There has been little evidence to suggest that the IL-6 -174G>C and IL-10 -1082A>G polymorphisms are significantly associated with susceptibility to celiac disease. Thus, we performed the present meta-analysis to explore the potential association between these polymorphisms and celiac disease risk. METHODS: Eligible studies were searched in PubMed, Medline, Embase, Web of Science and CNKI database up to April 20, 2019. Odds ratios with 95% confidence interval were calculated to assess the potential associations. Moreover, we performed the heterogeneity, sensitivity, and publication bias tests to clarify and validate the pooled results. RESULTS: Overall, nine case-control studies involving five studies with 737 cases and 1,338 control on IL-6 -174G>C polymorphism and four studies with 923 cases and 864 controls on IL-10 -1082A>G polymorphism were selected. The pooled ORs showed that the IL-6 -174G>C and IL-10 -1082A>G polymorphisms were not significantly associated with increased risk of celiac disease under all five genetic models. There was no publication bias. CONCLUSION: To the best of our knowledge, this is the first meta-analysis summarizing all of the available studies on the association of IL-6 -174G>C and IL-10 -1082A>G polymorphisms with celiac disease. Our results suggest that the IL-6 -174G>C and IL-10 -1082A>G polymorphisms may not be associated with increased risk of celiac disease. Moreover, large and well-designed studies are needed to fully describe the association of IL-6 -174G>C and IL-10 -1082A>G polymorphisms with celiac disease.

RESUMO CONTEXTO: Há poucas evidências para sugerir que os IL-6 -174G>C e IL-10 -1082A>G polimorfismos são significativamente associados com susceptibilidade para doença celíaca. Assim, foi realizada a presente meta-análise para explorar a potencial associação entre estes polimorfismos com o risco de doença celíaca. MÉTODOS: Foram pesquisados estudos elegíveis no Pubmed, Medline, Embase, Web of Science e CNKI Database até abril de 2019. Razões de probabilidades com 95% de intervalo de confiança foram calculados para avaliar as potenciais associações. Além disso, observou-se a heterogeneidade, a sensibilidade e o viés de publicação para esclarecer e validar os resultados agrupados. RESULTADOS: No total, nove estudos caso-controle envolvendo cinco estudos com 737 casos e 1.338 controle em IL-6 -174G>C polimorfismo e quatro estudos com 923 casos e 864 controles em IL-10 -1082A>G polimorfismo foram selecionados. As razões de probabilidade mostraram que o IL-6 -174G>C e IL-10 -1082A>G polimorfismos não estavam significativamente associados com aumento risco de doença celíaca nos cinco modelos genéticos. Não foi detectado viés de publicação. CONCLUSÃO: Pelo nosso conhecimento esta é a primeira meta-análise resumindo todos estudos disponíveis para associação de IL-6 -174G>C e IL-10 -1082A>G polimorfismos com doença celíaca. Estes resultados sugerem que os IL-6 -174G>C e IL-10 -1082A>G polimorfismos podem não ser associados com aumento risco de doença celíaca. Além disso, maiores estudos e mais bem desenhados são necessários para descrever totalmente a associação de IL-6 -174G>C e IL-10 -1082A>G polimorfismos com doença celíaca.

Polymorphism in the interleukin-10 gene is associated with overactive bladder phenotype associated with HTLV-1 infection

Abstract INTRODUCTION Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. METHODS We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants-rs3024496, rs1800871, rs1800896-and used logistic regression analysis to determine their association with clinical phenotypes. RESULTS No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28-0.70, p=0.001). CONCLUSIONS Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections.

Association of interleukin-10 -592a>c and -819t>c polymorphisms with gastric cancer risk: a systematic review and meta-analysis of 44 case-control studies / Associação de polimorfismos da interleucina-10 -592 a>c e -819 t> c com risco de câncer gástrico: revisão sistemática e metanálise de 44 estudos de caso-controle

ABSTRACT Introduction: A series of studies have evaluated the association between -592A>C and -819T>C polymorphisms in the promoter regions of Interleukin-10 (IL-10) and gastric cancer (GC) risk. However, the results remain inconclusive. Objective: To better understand the association of the polymorphisms with GC risk, we performed a comprehensive meta-analysis. Method: An electronic search was performed of several databases to identify relevant studies up to April 2018. Results: A total of 44 case-control studies, including 26 studies on IL-10 -592A>C (5,332 cases and 8,272 controls) and 18 studies on IL-10 -819T>C (3,431 cases and 6,109 controls) were selected. Overall, -592A>C polymorphism was associated with the risk of GC under the heterozygote model (OR=1.153, 95% CI=1.020-1.305, p=0.023), but not -819T>C polymorphism. When stratified by ethnicity, significant association was only observed in the Asians under the allele model (OR=1.153, 95% CI=1.007-1.320, p=0.040) and the heterozygote model (OR=1.218, 95% CI=1.076-1.379, p=0.002) for -592A>C. Conclusion: The current meta-analysis results inconsistent with previous meta-analyses; showed that the IL-10 -592A>C polymorphism, but not -819T>C polymorphism, may be contributed to the susceptibility of GC in overall and Asian populations.

RESUMO Introdução: Uma série de estudos avaliou a associação entre os polimorfismos -592A>C e -819T>C nas regiões promotoras do risco de interleucina-10 (IL-10) e câncer gástrico (GC). No entanto, os resultados permanecem inconclusivos. Objetivo: Para entender melhor a associação dos polimorfismos com o risco de GC, realizamos uma meta-análise abrangente. Método: Foi realizada busca eletrônica de vários bancos de dados para identificar estudos relevantes até abril de 2018. Resultados: Um total de 44 estudos caso-controle, incluindo 26 estudos sobre IL-10 -592A>C (5.332 casos e 8.272 controles) e 18 estudos sobre IL-10 -819T>C (3.431 casos e 6.109 controles) foram selecionados. No geral, o polimorfismo -592A> C foi associado ao risco de GC sob o modelo heterozigoto (OR=1,153, 95% IC=1,020-1,305, p=0,023), mas não polimorfismo -819T>C. Quando estratificada por etnia, associação significativa foi observada apenas nos asiáticos sob o modelo alelo (OR=1,153, IC 95%=1,007-1,320, p=0,040) e o modelo heterozigoto (OR=1,218, IC 95%=1,076-1,379, p=0,002) para -592A>C. Conclusão: Os atuais resultados são inconsistentes com metanálises anteriores; mostrou que o polimorfismo IL-10 -592A> C, mas não o polimorfismo -819T>C, pode ter contribuído para a suscetibilidade de GC em populações globais e asiáticas.

Associação de polimorfismos da região do promotor do gene interleucina-10 com susceptibilidade ao câncer colorretal: uma revisão sistemática e meta-análise / Association of promoter region polymorphisms of interleukin-10 gene with susceptibility to colorectal cancer: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Several epidemiological studies have investigated the association of promoter region polymorphisms of Interleukin-10 (IL-10) gene with colorectal cancer (CRC), while the conclusion is still conflicting and inconclusive. OBJECTIVE: We conducted this meta-analysis to evaluate the association of promoter region polymorphisms of IL-10 with CRC. METHODS: Eligible articles were identified by a search of several bibliographic databases for the period up to March 15, 2018. The strength of the association was measured by odd ratios with 95% confidence intervals. RESULTS: A total of 28 case-control studies with 5,647 CRC cases and 6,908 controls were selected, including 14 studies for IL-10 -1082A>G (rs1800896) polymorphism (2,702 cases and 3,649 controls), eleven studies for -592C>A (rs1800872) polymorphism (3,259 cases and 4,992 controls), and three studies for -819T>C (rs1800871) polymorphism (477 cases and 544 controls). By pooling all eligible studies, we found that the IL-10 -1082A>G and -592C>A polymorphisms were not associated with increased CRC risk in overall population. However, there was significant associations between the IL-10 -819T>C polymorphism and CRC susceptibility under the allele model (A vs G: OR=1.278, 95% CI 1.043-1.566, P=0.018) and the recessive model (AA vs AG+GG: OR=1.709, 95% CI 1.026-2.845, P=0.039). CONCLUSION: In this meta-analysis we found that IL-10 -819T>C polymorphism was associated with significantly increased risk of CRC; while the IL-10 -1082A>G and -592C>A polymorphisms were not associated with CRC risk. The IL-10 -819T>C polymorphism may be important as suspected predictive factor of CRC occurrence.

RESUMO CONTEXTO: Vários estudos epidemiológicos têm investigado a associação de polimorfismo da região promotora do gene interleucina-10 (IL-10) com câncer colorretal (CRC), mas por enquanto a conclusão ainda é conflitante e inconclusiva. OBJETIVO: Foi realizada esta meta-análise para avaliar a associação de polimorfismo da região promotora do Il-10 com o câncer colorretal. MÉTODOS: Os artigos elegíveis foram identificados por uma pesquisa de várias bases de dados bibliográficas para o período até 15 de março de 2018. A força da associação foi medida por odds ratio (OR) com intervalos de 95% de confiança (IC). RESULTADOS: Um total de 28 estudos de casos-controles com 5.647 casos de câncer colorretal e 6.908 controles foram selecionados, incluindo 14 estudos para o polimorfismo de IL-10-1082A>G (rs1800896) (2.702 casos e 3.649 controles), 11 estudos para-592C>A (rs1800872) polimorfismo (3.259 casos e 4.992 controles), e três estudos para-819T>C (rs1800871) polimorfismo (477 casos e 544 controles). Ao reunir todos os estudos elegíveis, verificou-se que o Il-10-1082A>G e-592C>A polimorfismo não foram associados com o aumento do risco de câncer colorretal na população global. No entanto, houve associações significativas entre o polimorfismo IL-10-819T>C e a susceptibilidade de câncer colorretal o modelo alelo (A vs G: OR=1,278; 95% CI 1,043-1,566; P=0,018) e o modelo recessivo (AA vs AG + GG: ou =1,709; 95% CI 1,026-2,845; P=0,039). CONCLUSÃO: Nesta meta-análise revelou-se que o polimorfismo IL-10-819T>C foi associado a um risco significativamente maior de câncer colorretal; enquanto o Il-10-1082A>G e-592C>A polimorfismos não foram associados com o risco de câncer colorretal. O polimorfismo IL-10-819T>C pode ser importante como fator preditivo suspeito da ocorrência de câncer colorretal.

Association of Interleukin-10 -1082A>G (rs1800896) Polymorphism with Predisposition to Breast Cancer: a Meta-Analysis based on 17 Case-Control Studies

SUMMARY INTRODUCTION The association between the between IL-10 -1082A>G (rs1800896) polymorphism and breast cancer has been evaluated by several number case-control studies. However, these studies might be underpowered to reveal the true association. OBJECTIVE We have performed a comprehensive meta-analysis to investigate the association IL-10 -1082A>G polymorphism and breast cancer. MATERIALS AND METHODS A systematic literature search was conducted using PubMed, Google Scholar, and Web of Science up to September 20, 2017. Data was analysed with CMA software to identify the strength of the association by pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS A total of 17 case-control studies involving 3275 cases and 3416 controls obtained from database searches were examined. Overall, there was no significant association between IL-10 -1082A>G polymorphism and breast cancer risk under all genetic models. No significant publication bias was found for the five genetic models (G vs. A OR = 1.184, 95% CI = 0.895-1.180, p= 0.230; GG vs. AA: OR = 1.430, 95% CI = 0.927-2.204, p= 0.106; GA vs. AA: OR = 0.966, 95% CI = 0.765-1.221, p= 0.774; GG+GA vs. AA: OR = 0.957, 95% CI = 0.697-1.314, p= 0.786; and GG vs. GA+AA: OR = 1.221, 95% CI = 0.981-1.518, p= 0.073). Moreover, there was no significant association between the IL-10 -1082A>G polymorphism and breast cancer risk by ethnicity. CONCLUSION Our findings indicated that IL-10 -1082A>G (rs1800896) polymorphism might not be a risk factor for the development of breast cancer.

RESUMO

Associação de interleucina-10-1082A/polimorfismo G (rs1800896) com suscetibilidade a câncer gástrico: meta-análise de 6. 101 casos e 8. 557 controles / Association of interleukin-10 -1082 a/g (rs1800896) polymorphism with susceptibility to gastric cancer: meta-analysis of 6, 101 cases and 8, 557 controls

ABSTRACT BACKGROUND: The promoter -1082 A/G (rs1800896) polymorphism of Interleukin-10 (IL-10) gene have been widely reported and considered to have a significant role on gastric cancer risk, but the results are inconsistent. OBJECTIVE: To clarify the association, we conducted a meta-analysis to investigate the associations IL-10 -1082 A/G polymorphism with gastric cancer. METHODS: Eligible articles were identified by searching databases including PubMed, Web of Science, and Google Scholar up to August 03, 2017. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. RESULTS: A total of 30 case-control studies with 6,101 cases and 8,557 controls were included in this meta-analysis. Overall, a significant association between IL-10 -1082 A/G polymorphism and gastric cancer risk was observed under the allele model (G vs A: OR=1.305, 95% CI=1.076-1.584; P=0.007), heterozygote model and (GA vs AA: OR=1.252, 95% CI=1.252-1.054; P=0.011) and dominant model (GG+GA vs AA: OR=1.264, 95% CI=1.053-1.516; P=0.012). In the subgroup analysis by ethnicity, increased gastric cancer risk were found in Asians under the allele model (G vs A: OR=1.520, 95% CI=1.172-1.973; P=0.002), homozygote model (GG+GA vs AA: OR=1.571, 95% CI=1.023-2.414; P= 0.039), heterozygote model (GA vs AA: OR=1.465, 95% CI=1.192-1.801; P≤0.001) and dominant model (GG+GA vs AA: OR=1.448, 95% CI=1.152-1.821; P=0.002), but not among Caucasian and Latinos populations. CONCLUSION: These results suggested that the IL-10 -1082 A/G (rs1800896) polymorphism might contribute to the gastric cancer susceptibility, especially among Asians.

RESUMO CONTEXTO: O promotor-1082 A/polimorfismo G (rs1800896) do gene da interleucina-10 (IL-10) é amplamente relatado e considerado por ter um papel significativo no risco de câncer gástrico, porém os resultados são inconsistentes. OBJETIVO: Para esclarecer melhor esta associação, realizou-se uma meta-análise para investigar as associações de IL-10-1082 A/polimorfismo G com câncer gástrico. MÉTODOS: Artigos elegíveis foram identificados através de pesquisa de bases de dados PubMed, Web of Science e Google Scholar até 3 de agosto de 2017. Razões de possibilidades (OR) com intervalo de confiança de 95% correspondente (CIs) foram usados para avaliar a associação. RESULTADOS: Um total de 30 estudos de caso-controle, 6.101 casos e com 8.557 controles foram incluídos nesta meta-análise. Em geral, uma associação significativa entre IL-10-1082 A/G polimorfismo e risco de câncer gástrico foi observada sob o modelo de alelo (G vs A: OR=1.305, 95% CI=1.076-1.584; P=0.007), no modelo heterozigoto (GA vs AA: OR=1.252, 95% CI=1.252-1.054; P=0.011) e modelo dominante (GG+GA vs AA: OR=1.264, 95% CI=1.053-1.516; P=0.012). Na análise de subgrupo pela etnia, foi encontrado risco aumentado de câncer gástrico em asiáticos sob o modelo de alelo (G vs A: OR=1.520, 95% CI=1.172-1.973; P=0.002), modelo heterozigoto (GG+GA vs AA: OR=1.571, 95% CI=1.023-2.414; P= 0.039), e modelo dominante (GG+GA vs AA: OR=1.448, 95% CI=1.152-1.821; P=0.002), mas não entre a população caucasiana e latina. CONCLUSÃO: Estes resultados sugeriram que a IL-10-1082 A/polimorfismo G (rs1800896) pode contribuir para a suscetibilidade de câncer gástrico, especialmente entre os asiáticos.

Interleukin-6 and interleukin-10 gene polymorphisms and the risk of further periodontal disease progression

Abstract: Susceptible genotypes to periodontal disease are associated with disease onset and progression. The aim of this study was to examine the effect of gene polymorphisms on the risk of further disease progression and the need for further treatment among adults with chronic periodontal disease. Sixty-seven patients diagnosed with chronic periodontitis were grouped according to genotype status and risk of further progression of disease and tooth loss. All individuals were clinically evaluated for probing pocket depth, clinical attachment loss and bleeding on probing at baseline and 45 days after treatment. Blood samples were collected at baseline and genotyping of the polymorphisms in IL-6 (rs1800796) and IL-10 (rs1800872) genes were performed by PCR. Following DNA separation and genotyping, 65.7% of the patients were homozygous carriers of the IL-6 −572G and 49.3% were carriers of the IL-10 −592A allele. Individuals at risk of disease progression ranged from 7.5% to 62.7% based on the criteria used. Carriers of the IL-10 −592A allele were significantly associated with BOP ≥ 30% and therefore exhibited a higher risk of further periodontal breakdown (p = 0.018) with an odds ratio of 1.18. None of the other definitions of disease progression were significantly associated with the examined IL-6 and IL-10 genotypes (p > 0.05). IL-10 polymorphism was associated with an increased risk of further disease progression and the potential need for further treatment following non-surgical periodontal treatment. Susceptible IL-6 genotypes were not associated with the risk of persisting or recurrent disease activity.

IL-6, TNF-α, and IL-10 levels/polymorphisms and their association with type 2 diabetes mellitus and obesity in Brazilian individuals

ABSTRACT Objective This study aimed to investigate the association of plasma TNF-α, IL-6, and lL-10 levels and cytokine gene polymorphisms [TNF-α (-308 G→A), IL-6 (-174 C→G) and IL-10 (-1082 A→G, -819 T→C and -592 A→C)] in type 2 diabetes mellitus (T2DM) and obese patients. Subjects and methods One hundred and two T2DM patients and 62 controls were included in this study. Cytokine plasma levels were measured by the Cytometric Bead Array method. Genotyping was carried out by the polymerase chain reaction. Results IL-6 levels were significantly different between T2DM patients and controls. Interestingly, IL-6 levels were higher in T2DM patients with BMI > 30 kg/m2 compared with other patients and obese controls. The genotype and allele frequencies were similar between patients and controls. In the T2DM group, the SNP IL-10 -819 T/C showed a difference between the cytokine level and genotypes: IL-10 level in the TT genotype was significantly higher when compared to CC genotype. Conclusions These results suggest an association between IL-6 levels and obesity, and IL-10 levels and the SNP -819 T/C in T2DM. Knowledge of these variants in T2DM might contribute to a better understanding of the role of inflammation in the etiology and progression of this disease.

Alzheimer's disease and cytokine IL-10 gene polymorphisms: is there an association? / A doença de Alzheimer e os polimorfismos no gene da citocina IL-10: há alguma associação?

ABSTRACT Alzheimer's disease (AD) is the most common form of dementia. In the last 15 years, a new theory has proposed the autoimmune mechanism as a trigger for AD. Studies on the association between AD and inflammatory biomarkers have yielded controversial results. Interleukin-10 (IL-10), an anti-inflammatory mediator, has been pointed out as one of the main cytokines associated with the occurrence of AD. Moreover, treatment that increases IL-10 levels could be a potential therapy for AD, since this cytokine acts on amyloid and pro-inflammatory molecule reduction. Based on the current literature, this study reviews evidence regarding the role of IL-10 polymorphisms in the context of AD, which has been shown to be of paramount importance for attenuating neuroinflammation, cognitive dysfunction and neurodegeneration.

RESUMO A doença de Alzheimer (DA) é a forma mais comum de demência. Nos últimos 15 anos, uma nova teoria propõe um mecanismo autoimmune como o gatilho para a DA. Associações entre DA e biomarcadores inflamatórios têm sido registradas, contudo com resultados controversos. A interleucina-10 (IL-10), um mediador anti-inflamatório, tem sido apontada como uma das principais citocinas associadas com a ocorrência de DA. Além disso, os tratamentos que aumentam os níveis de IL-10 podem ser uma terapia potencial para DA, uma vez que esta citocina atua sobre a redução de substância amiloide e de moléculas pró-inflamatórias. Baseando-se em literaturas atuais, este estudo revisa evidências relacionadas com o papel da IL-10 e seus polimorfismos no contexto da DA, o qual se mostrou ser de fundamental importância para atenuar a neuroinflamação, a disfunção cognitiva e a neurodegeneração.

IL-6 and IL-10 gene polymorphisms in patients with aggressive periodontitis: effects on GCF, serum and clinic parameters

Abstract Genetic variations observed in cytokines affect periodontitis susceptibility. The aim of this study was to investigate interleukin(IL)-6(-174) and IL-10(-597) gene polymorphisms in generalized aggressive periodontitis (GAgP) patients. Also, we aimed to evaluate the effects of IL-6 and IL-10 gene polymorphisms on the clinical outcomes of non-surgical periodontal therapy and cytokine levels in gingival crevicular fluid(GCF) and serum. Fifty-three patients with GAgP and 50 periodontally healthy individuals were included in this study. Clinical parameters, GCF and blood samples were collected at baseline and at 6-week. Non-surgical periodontal therapy was performed in patients with GAgP. Gene analysis were determined by PCR-RFLP(polymerase chain reaction-restriction fragment length polymorphism) and cytokine levels were determined by enzyme-linked immunosorbent assay(ELISA).GAgP patients showed significant improvement on clinical parameters after periodontal therapy(p<0.05). In the GAgP group, IL-6 GG genotype and G allele frequency were higher than in the control group. GCF IL-6 level was also significantly lower at 6-week in the GAgP group. Higher GCF IL-10 levelswere observed in patients carrying the IL-6 GG genotype than in those carrying the GC+CC genotype at baseline. In conclusion, IL-6(-174) and IL-10(-597) gene polymorphisms were found to be associated with GAgP and genotype distribution did not affect the outcome of non-surgical periodontal therapy, while patients with IL-6(-174) GG genotype had higher levels of GCF IL-10 levels.

There is no evident correlation between interleukin-10 gene polymorphisms and periportal fibrosis regression after specific treatment

Abstract INTRODUCTION: We evaluated the associations between interleukin-10 (IL-10) gene polymorphisms -G1082A/-C819T/-C592A and periportal fibrosis regression after specific treatment for schistosomiasis. METHODS: This retrospective cohort study involved 125 Brazilian patients infected with Schistosomiasis mansoni, who were followed up for 2 years after specific treatment to estimate the probability of periportal fibrosis regression. RESULTS: There was no evidence of associations between IL-10 polymorphisms and periportal fibrosis regression after treatment. CONCLUSIONS: There was no evidence of associations between gene promoter polymorphisms of IL-10 and the regression of periportal fibrosis in this Brazilian population.

Analysis of polymorphisms in Interleukin 10, NOS2A, and ESR2 genes in chronic and aggressive periodontitis

Abstract The objective of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in the IL10, NOS2A, and ESR2 genes and chronic periodontitis (CP) and aggressive periodontitis (AgP). Three groups of patients underwent periodontal and radiographic evaluations: CP (n = 61), AgP (n = 50), and periodontally healthy (control group=61). Genomic DNA was extracted from oral epithelial cells and used for genotyping by real-time polymerase chain reaction using TaqMan® probes. The investigated SNPs were: -1087G > A, -819C > T and -592C > A in the IL10; +2087G > A in the NOS2A, and +1730G > A in the ESR2 gene. Differences in genotype and allele frequencies of each polymorphism and some individual characteristics were analyzed using the chi-square test and multivariate logistic regression analysis. Analysis of SNPs and haplotypes in the IL10 and SNP in the ESR2 gene did not present any significant association with AgP or CP. The +2087G allele of the NOS2A gene tended to be significantly associated with periodontal disease. Patients carrying the genotype +2087GG in the NOS2A gene were genetically protected against the development of CP (p = 0.05; OR = 0.44; 95%CI = 0.20-0.95). This result showed greater significance when patients with AgP and CP were combined (total PD) (p = 0.03; OR = 0.46; 95%CI = 0.23-0.92). In conclusion, the studied Brazilian population had a significantly higher frequency of the GG genotype for the +2087 SNP in the NOS2A gene in individuals without periodontitis, although statistical significance was not maintained after multiple logistic regression.

Associations between Single Nucleotide Polymorphisms of High Mobility Group Box 1 Protein and Clinical Outcomes in Korean Sepsis Patients

PURPOSE: High mobility group box 1 (HMGB1) plays a central role in the pathogenesis of sepsis and multiple organ dysfunction syndromes. We investigated the associations of a single nucleotide polymorphism (SNP; rs1045411) in HMGB1 with various clinical parameters, severity, and prognosis in patients with sepsis, severe sepsis, or septic shock. MATERIALS AND METHODS: We enrolled 212 adult patients followed for 28 days. All patients were genotyped for rs1045411, and the serum levels of HMGB1 and several cytokines were measured. RESULTS: The proportions of patients according to genotype were GG (71.2%), GA (26.4%), and AA (2.4%). Among patients with chronic lung disease comorbidity, patients with a variant A allele had higher positive blood culture rates and higher levels of various cytokines [interleukin (IL)-1beta, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha] than those with the GG genotype. In the analysis of those with diabetes as a comorbidity, patients with a variant A allele had higher blood culture and Gram-negative culture rates than those with GG genotypes; these patients also had a higher levels of IL-17. In the analysis of those with sepsis caused by a respiratory tract infection, patients with a variant A allele had higher levels of IL-10 and IL-17 (all p<0.05). This polymorphism had no significant impact on patient survival. CONCLUSION: The variant A allele of rs1045411 appears to be associated with a more severe inflammatory response than the GG genotype under specific conditions.