IL-10 Gene Polymorphisms Research Articles

Evaluation of IL-6 and IL-17A gene polymorphisms in Iraqi patients infected with COVID-19 and type 2 diabetes mellitus.

In patients with COVID-19, diabetes mellitus type 2 (T2DM) increases the risk of hospitalization and death. Patients who have IL-6 and IL-17A single nucleotide polymorphisms (SNPs) are more likely to have severe COVID-19. This study aims to determine whether SNPs of the IL-6 gene at rs1800795 (G > C) and the IL-17A gene at rs2275913 (G > A) are associated with COVID-19 and T2DM in the Iraqi population. Twenty-four people were divided into 4 groups as follows: six patients with severe COVID-19 and T2DM were placed in Group 1 as "G1", six patients with COVID-19 but no T2DM were placed in Group 2 as "G2", and six patients with T2DM were placed in Group 3 as "G3". There were also six healthy controls included in each group. Polymerase chain reaction (PCR) was used to amplify the target genes after genomic DNA from the blood samples was extracted. Sanger sequencing was used to find the SNPs in both the forward and reverse directions for each sample. In the case of IL-6 SNP at rs1800795, the GG genotype was more common in "G3", the CC genotype was less common in all patient groups than in controls, and the GC allele was more common in "G2" than in the control group. In comparison to the controls, the three patient groups showed lower frequencies of the C allele and higher frequencies of the G allele. Regarding IL-17A gene polymorphism, the AA and GA genotypes were more prevalent in "G2" and "G3", respectively. The GG genotype and G allele frequency dropped in all patient groups compared to the control group, whereas the A allele frequency increased in all patient groups. The IL-6 gene at rs1800795 (G/C) and the IL-17A gene at rs2275913 (G/A) loci were associated with COVID-19 and T2DM in Iraqi population.

Association between IL-10 gene polymorphisms (− 1082 A/G, -819 T/C, -592 A/C) and hepatocellular carcinoma: a meta-analysis and trial sequential analysis

BackgroundThe carcinogenesis of hepatocellular carcinoma is complicated, and genetic factor may have the role in the malignant transformation of liver cells. IL-10 gene polymorphisms have been investigated for their potential roles in hepatocellular carcinoma This study aimed to investigate the relationship between polymorphisms of IL-10 (-1082 A/G, -819 T/C, -592 A/C), and hepatocellular carcinoma by performing a meta-analysis with eligible individual studies.MethodsThis study followed the PRISMA 2020 Checklist. Relevant studies were searched in health-related databases. The Newcastle-Ottawa Scale criteria were used to evaluate the studies quality. Pooled odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and hepatocellular carcinoma using five genetic models. Stratification was done by ethnic groups. Trial sequential analysis (TSA) was performed to determine the required information size.ResultsFifteen case-control studies (n = 8182) were identified. Overall, the heterozygous model showed a marginal significant association only between IL-10 (-1082 A/G) and hepatocellular carcinoma risk (OR: 0.82, 95% CI: 0.67-1.00, 9 studies). On stratification, IL-10 (-1082 A/G) was significantly associated with hepatocellular carcinoma risk in the non-Asian population under dominant (OR: 0.62, 95% CI: 0.45–0.86, 4 studies), heterozygous (OR: 0.60, 95% CI: 0.43–0.85) and allelic models (OR: 0.79, 95% CI: 0.64–0.99). IL-10 (-819 T/C) was significantly associated with hepatocellular carcinoma risk only among non-Asians under the dominant (OR: 1.47, 95% CI: 1.02–2.13, 8 studies), recessive (OR: 1.99, 95% CI: 1.03–3.86, and homozygous models (OR: 2.18, 95% CI: 1.13–4.23). For IL-10 (-592 A/C) with 11 studies, there was no significant association with hepatocellular carcinoma in all five genetic models (P values > 0.5). TSA plots indicated that the information size for firm evidence of effect was sufficient only for the analysis of IL-10 (-592 A/C), but not for the − 1082 A/G or -819 T/C.ConclusionsFindings suggest that IL-10 (-1082 A/G and − 819 T/C) polymorphisms are associated with hepatocellular carcinoma in ethnic-specific manner. However, this evidence is not conclusive because the sample size was insufficient. IL-10 (-592 A/C) polymorphism was not associated with hepatocellular carcinoma albeit with sufficient information size. Future well-designed large case-control studies on IL-10 (-1082 A/G and − 819 T/C) with different ethnicities are recommended.

Interleukin-18, Interleukin-18 Gene Polymorphisms and Interleukin18 Binding Protein in Children and Adolescents with Immune Thrombocytopenia

Background Immune thrombocytopenia (ITP) is an autoimmune illness characterized by an aberrant T cell response, which is supported by autoreactive B cell growth and differentiation. IL-18 expression has been linked to a number of autoimmune and inflammatory illnesses. IL18BP is a protein that binds IL-18 with high affinity, suggesting a potential mechanism for regulating IL-18 activity. Corticosteroids may play a significant role in reversing the IL-18- IL18BP ratio by upregulating IL18BP. Objective The aim was to study associations between IL-18 and two associated gene polymorphism sites -607 & -137 with incidence and response to therapy in patients with ITP. Patients and Methods It is a case control study conducted on children and adolescents with ITP.A total of 55 patients with different stages of ITP (25 acute, 18 persistent & 12 chronic patients) were recruited with 30 age matched healthy controls. All patients were subjected to full history and physical examination. Laboratory investigations included serial blood counts, IL-18 and IL-18BP serum levels using enzyme linked immunosorbent assay (ELISA) and IL-18 gene polymorphisms using polymerase chain reaction (PCR). Results At diagnosis the median platelet count was 16× 109/L (range 2-79) & eventually increased to a median of 90× 109/L after treatment. IL-18 level was significantly higher than that of control (P < 0.001) & even after treatment. There was no significant difference between patient and control groups regarding the studied gene polymorphism sites -607 & -137. The mean IL-18 was still significantly elevated in all stages of ITP compared to control group & as well the drop after treatment. This was also observed in IL-18 BP which increased significantly after response to steroid therapy. However, it was observed that the decline in level of IL-18 as well as increment in IL-18 BP was the least in the patients tested during the acute phase. Mean IL-18 & IL-18 BP levels show no significant relation with gender, family history of ITP, mode of treatment or genotype. Conclusion Among the studied IL-18 gene polymorphisms, no significant difference was detected among ITP patients or had a significant correlation with clinical or laboratory markers. Reversed IL-18/IL-18BP ratio is an important modulator in pathogenesis of ITP. Increasing levels of IL-18BP could have a significant role in treatment.

Association of IL4RA and IL-8 polymorphism in predicting susceptibility to tuberculosis.

Mycobacterium tuberculosis causes an infectious bacterial disease frequently affecting the lungs. With two fatalities from tuberculosis (TB) occurring every three minutes, India has the highest disease burden. The etiology of TB has been linked to IL-8 and IL-4RA. Thus, the impact of the IL4RAQ576R and IL8 gene polymorphisms on TB susceptibility was assessed. 301 healthy and 301 TB patients participated in a cross-sectional study. Polymerase chain reaction-restriction fragment length polymorphism was performed to identify the genotype of the IL4RAQ576R and IL-8 +781 C/T gene polymorphism. The odds ratio and 95% confidence intervals were calculated using logistic regression to evaluate the risk of TB with IL4RAQ576R and IL-8 +781 C/T polymorphism. A significant association was found between IL-4RA (p=0.04) and IL-8 +781 C/T (p=0.03) in TB. Further, when clinical symptoms were compared with both polymorphisms, two of them, i.e., cough in IL-4RA576R (p=0.04) and breathlessness (p=0.01) in IL-8 +781 C/T, showed a significant association. Moreover, different combinations of the single nucleotide polymorphisms (SNPs) were made, and the 3-risk allele shows a significant protective role (p=0.02). There is considerable evidence showing that M. tuberculosis causes TB, an infectious disease that is genetically predisposed. The results of our study also showed that IL-4 RA Q576R and IL-8 +781 C/T played a significant protective function against TB, confirming the claim mentioned earlier. However, only the cough in IL-4RA576R and the dyspnea in IL-8 +781 C/T exhibited a significant co-relation in TB patients when symptoms were examined. Additionally, the combined effects of the two SNPs were investigated, and it was discovered that the 3-risk allele has a strong association with TB. Therefore, the polymorphisms mentioned earlier, which may also be influenced by ethnicity, may significantly impact the chance of developing TB.

IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children

Genetic factors play a crucial role in the immune response of juvenile idiopathic arthritis (JIA) and juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to investigate the association of IL12B (rs3212227, rs6887695) and IL17 (rs2275913, rs763780) gene polymorphisms with the susceptibility of JIA and JSLE in Chinese children. A total of 303 healthy controls and 304 patients including 160 JIA and 144 patients were analyzed, and the genetic polymorphisms were genotyped by using a Sequenom MassArray system. There was a significant association between the IL12B rs3212227 genotype and the increased risk of JSLE (P = .01). For rs6887695, the minor allele C was significantly associated with the increased risk of JIA (odds ratio = 1.48, 95% confidence interval [CI] = 1.12–1.95, P = .005). Moreover, rs6887695 genotype was significantly associated with both JIA and JSLE susceptibility (P < .05). Besides, IL12B haplotype GC significantly associated with the increased risk of JIA (P = .016). However, no significant difference was found between the IL17 (rs2275913, rs763780) gene polymorphisms and JIA or JSLE susceptibility (P > .05). And similar genotype distributions of IL12B and IL17 polymorphisms were found between the patients with nephritis and without nephritis in JSLE (P > .05). Our results indicated that IL12B polymorphisms was associated with an increased risk for the development of JIA and JSLE in Chinese children, highlighting the involvement of inflammation in the pathogenesis of JIA and JSLE. Moreover, there was a risk haplotype in IL12B which could increase the risk of JIA.

Association between polymorphisms of IL4, IL13, IL10, STAT6 and IFNG genes, cytokines and immunoglobulin E levels with high burden of Schistosoma mansoni in children from schistosomiasis endemic areas of Cameroon.

Eliminating schistosomiasis as a public health problem by 2030 requires a better understanding of the disease transmission, especially the asymmetric distribution of worm burden in individuals living and sharing the same environment. It is in this light that this study was designed to identify human genetic determinants associated with high burden of S. mansoni and also with the plasma concentrations of IgE and four cytokines in children from two schistosomiasis endemic areas of Cameroon. In school-aged children of schistosomiasis endemic areas of Makenene and Nom-Kandi of Cameroon, S. mansoni infections and their infection intensities were evaluated in urine and stool samples using respectively the Point-of-care Circulating Cathodic Antigen test (POC-CCA) and the Kato Katz (KK) test. Thereafter, blood samples were collected in children harbouring high burden of schistosome infections as well as in their parents and siblings. DNA extracts and plasma were obtained from blood. Polymorphisms at 14 loci of five genes were assessed using PCR-restriction fragment length polymorphism and amplification-refractory mutation system. The ELISA test enabled to determine the plasma concentrations of IgE, IL-13, IL-10, IL-4 and IFN-γ. The prevalence of S. mansoni infections was significantly higher (P<0.0001 for POC-CCA; P=0.001 for KK) in Makenene (48.6% for POC-CCA and 7.9% for KK) compared to Nom-Kandi (31% for POC-CCA and 4.3% for KK). The infection intensities were also higher (P<0.0001 for POC-CCA; P=0.001 for KK) in children from Makenene than those from Nom-Kandi. The allele C of SNP rs3024974 of STAT6 was associated with an increased risk of bearing high burden of S. mansoni both in the additive (p=0.009) and recessive model (p=0.01) while the allele C of SNP rs1800871 of IL10 was protective (p=0.0009) against high burden of S. mansoni. The alleles A of SNP rs2069739 of IL13 and G of SNP rs2243283 of IL4 were associated with an increased risk of having low plasma concentrations of IL-13 (P=0.04) and IL-10 (P=0.04), respectively. This study showed that host genetic polymorphisms may influence the outcome (high or low worm burden) of S. mansoni infections and also the plasma concentrations of some cytokines.

Association of interleukin-4 in patients with recurrent aphthous stomatitis

Abstract Background: Recurrent aphthous stomatitis (RAS) is a frequent ulcerative inflammatory disorder of the mouth. Various localized, systemic, and immunologic factors have quite a function in oral tolerance, although the etiology of RAS remains unexplained. The previous studies suggest that there is a significant association (interleukin-4—IL-4) level between in case and control group with RAS in saliva, and no significant difference between IL-4 rs 2243266 gene polymorphism with RAS. Objectives: To determine the level of IL-4 in saliva and the association of IL-4 gene polymorphism with the incidence of RAS. Materials and Methods: The subjects enrolled in the present study were (80) subjects of both genders. The age range was from 20 to 60 years. This study is carried out to detect the association of IL-4 level with RAS by enzyme-linked immunosorbent assay (ELISA) test and polymerase chain reaction (PCR) technique in Babylon Province, Iraq. The study sample consists of (80) subjects of both genders. The samples were divided into two groups including the patient group, (40) samples (female 21 and male 19) with RAS, and the control group (C) included (40) samples (20 females and males 20). Results: The results of the association between IL-4 level with RAS showed a significant association while the result of PCR sequencing found that there was no significant association of AG genotype of rs 2243266 with RAS with odd ratio 1.169 (0.54–2.54) 0.855 (0.39–1.86) and P-value 0.693. Conclusion: Females were more affected by RAS than males. There was a significant difference in IL-4 levels between the case and control groups.

Асоціація поліморфізмів генів GSTP1(A313G), MTHFR (С677T) та IL-10 (C819T) із ризиком виникнення гліобластоми

гліобластома одна з найбільш поширених злоякісних пухлин головного мозку з вкрай низькою виживаністю. Незважаючи на досягнення у вивченні молекулярного патогенезу та біології пухлин мозку, причини виникнення гліобластоми залишаються нез’ясованими. Дослідження останніх років вказують, що зміни у генах, які беруть участь у проліферації, диференціації та апоптозі клітин, можуть впливати на ризик виникнення онкологічних захворювань. Тож метою роботи було дослідити поліморфізми генів GSTP1(A313G), MTHFR (С677Т) та IL-10 (C819T) у хворих на гліобластому та проаналізувати їх зв’язок із ризиком розвитку цієї патології. Біологічним матеріалом для аналізу поліморфізмів генів GSTP1, MTHFR та IL-10 слугувала периферична кров хворих на гліобластому та практично здорових людей. Дослідження поліморфізмів генів проводилось за допомогою методу алель-специфічної ПЛР із використанням власних пар детекторів TaqMan MGB на основі флуоресцентних барвників, що призначені для виявлення однонуклеотидних замін. Встановлено, що частота мутантного алеля G гена GSTP1 у хворих становила 53,6% проти 32% у групі практично здорових людей. Розподіл генотипів гена GSTP1 у групі хворих відповідав закону генетичної рівноваги Харді-Вайнберга та статистично відрізнялась від показника у групі практично здорових людей і становив 0,538 проти 0,320 (χ2 = 13,10, р = 0,003). Визначено, що ризик виникнення гліобластоми є в 4,88 разів вищим у осіб, що є гомозиготними носіями мутантного алелю гена GSTP1 (генотип G313G) у порівнянні з іншими поліморфними варіантами. В результаті наших досліджень, було встановлено, що частота мутантного алеля С гена IL-10 у хворих становила 48,8%, що значно перевищує відповідний показник у групі практично здорових людей – 25%. Встановлено, що розподіл генотипів гена IL-10 у групі хворих відповідав закону генетичної рівноваги Харді-Вайнберга, частота мутантного алеля С гена IL-10 статистично відрізнялась від показника у групі практично здорових людей та становила 0,488 проти 0,250 (χ2 = 18,32, р = 0,00002). Встановлено, що існує асоціація між поліморфізмом гена IL-10 (C819T) та ризиком виникнення гліобластоми, у гомозиготних носіїв із генотипом Т819Т, ризик захворіти збільшується у 6,40 рази. Також нами було встановлено, що частота мутантного алелю Т гена MTHFR у хворих становила 35,0% проти 28,1% у групі практично здорових людей. Розподіл генотипів гена MTHFR у групі хворих відповідав закону генетичної рівноваги Харді-Вайнберга, а розподіл частот поліморфних варіантів ген показав відсутність статистично достовірних відмінностей між групою хворих та групою практично здорових людей (χ2 = 1,43 р = 0,23). Не було встановлено асоціації між поліморфізмом гена MTHFR (С677Т) і ризиком виникнення гліобластоми.

IL-4 and its polymorphism (&lt;i&gt;IL4&lt;/i&gt;-589C/T) in cervical neoplasia

The transition of cervical neoplasia (CIN) to cervical cancer occurs with the active participation of IL-4, for which both pro- and antitumor effects have been shown with tumors of various localizations. The expression of cytokines is regulated at the transcriptional level in the promoter region of the gene. It has been shown that the genotype IL4 (589C/T) (rs2243250) is associated with the development of gastric and breast cancer. The contribution of IL-4 genotypic variations to the development of CIN has not yet been studied. The aim of the study was to assess the risk of developing cervical neoplasia by the presence polymorphism of IL4 (589C/T) and the level of IL-4. The object of the study was circulating neutrophils, serum and genomic DNA of 36 patients with CIN and 20 women without dysplasia (comparison group). Using ELISA, the level of IL-4 was determined in neutrophil lysate and serum. Phagocytic activity and adhesive ability (CD11b) of neutrophils were assessed. Allele-specific real-time PCR using Taq-Man probes was used to analyze of the IL4 589C/T (rs2243250). Statistical processing was carried out using Statistica 13 and Jamovi 1.6.5.0. As a result of the study, it was found that the level of IL-4 in serum and circulating neutrophils in patients with CIN is significantly higher than in the comparison group. The -589C* allele of the IL4 gene and the TT genotype are more common in the group with CIN (55.5%) than in the control (25%). At the same time, a direct relationship was established between the presence of polymorphism and increased adhesive ability and with indicators of the phagocytic number of circulating neutrophils. Analysis of the incidence of IL4 C589T by the «case-control» method showed that the chances of CIN formation in carriers of the -589C allele and the TT genotype were 3.75 (95% CI: 1.013 - 13.880, Chi-square = 4.161, p = 0.042). The -589C* allele and TT IL4 genotype, neutrophil and serum IL-4 levels are associated with HPV infection. Using a binary logistic regression model, we demonstrated the possibility of using IL-4 levels in circulating neutrophils and IL-4 gene polymorphism (589C/T) for the differential diagnosis of patients with CIN (χ2 = 15.6, p = 0.001). Significant significance for their combination was assessed by ROC-curve analysis (IL-4 in neutrophils; IL4 (-589С*), 75% probability. Thus, the IL4 (589C/T) is associated with the adhesive and phagocytic activity of circulating neutrophils. In HPV-infected patients, IL4 gene polymorphism (589C/T) can serve as a marker for early detection and prognosis of CIN.

Systemic review and meta-analysis of the association between interleukin-10 and Takayasu arteritis.

The aim of this meta-analysis is to investigate the relationship between interleukin (IL)-10 levels and its polymorphism and Takayasu arteritis (TAK). Five databases including PubMed, Web of Science, Ovid, Sinomed and China National Knowledge Infrastructure (CNKI) were gone through from inception to March 31, 2022. Studies were screened according to the inclusion and exclusion criteria. Newcastle-Ottawa Scale (NOS) was applied to assess study quality. Strengths of association were evaluated by odds ratio (OR) and 95% CI. The T v. t (allele contrast), TT v. tt (homozygous contrast), Tt vs tt (heterozygous contrast), TT + Tt vs tt (dominant contrast) and TT vs Tt + tt (recessive contrast) models were adopted. Seven studies were included. No significant relationship between IL-10 and TAK was detected in the included patients (P > 0.05). The levels of IL-10 were lower in the active group than those in the stable group, which was -0.47 (95% CI: -0.93, 0.00) (P = 0.05). No significant relationships between IL-10 and TAK were found under all contrasts for polymorphisms rs1800871, rs1800872 and rs1800896 (P > 0.05). There was no significant difference in IL-10 levels between TAK patients and control subjects. The levels of IL-10 were lower in TAK patients in the active stage. There was no significant association between IL-10 gene polymorphisms and TAK. Further well-designed studies with larger sample sizes in patients with different stages are needed.

Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis.

The relationship between interleukin (IL)-10 and IL-6 gene polymorphisms and squamous cell carcinoma (SCC) has been demonstrated but with inconsistent conclusions. The aim of this study was to evaluate the potential associations of IL gene polymorphisms and the SCC risk. PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Database, WanFang, and China Science and Technology Journal Database databases were searched for articles reporting the correlations of IL-10 and IL-6 gene polymorphisms with the SCC risk. Odds ratio and 95% confidence interval were calculated using Stata Version 11.2. Meta-regression, sensitivity, and publication bias were analyzed. False-positive reporting probability and Bayesian measure of the false-discovery probability were used to explore the credibility of the calculation. Twenty-three articles were included. The IL-10 rs1800872 polymorphism showed a significant correlation with the SCC risk in the overall analysis. Studies pooled by ethnicity revealed that the IL-10 rs1800872 polymorphism reduced the SCC risk in the Caucasian population. The results of this study suggest that the IL-10 rs1800872 polymorphism may confer a genetic susceptibility to SCC, particularly oral SCC, in Caucasians. However, the IL-10 rs1800896 or IL-6 rs1800795 polymorphism was not significantly associated with the SCC risk.

Study of pathological and biochemical connection of IL-10 gene polymorphism and Rheumatoid Arthritis and Atopic Dermatitis in Egyptian patients admitted in local clinical setting

Study of pathological and biochemical connection of IL-10 gene polymorphism and Rheumatoid Arthritis and Atopic Dermatitis in Egyptian patients admitted in local clinical setting

Association between interleukin-2 (rs2069762) gene polymorphism and FVIII inhibitor development in Indonesian patients with severe hemophilia A

BACKGROUND Factor VIII (FVIII) inhibitors in hemophilia A (HA) patients render FVIII replacement therapy ineffective. Although its development cause is unclear, it has been classified into therapeutic and genetic-related etiologies. Single nucleotide polymorphisms (SNPs) in several cytokine genes, including interleukin (IL)-2, could increase the risk of FVIII inhibitor development. This study aimed to evaluate the association between IL-2 (rs2069762) gene SNP and FVIII inhibitor development in Indonesian patients with severe HA.&#x0D; METHODS The IL-2 (rs2069762) gene SNP was examined in 119 HA patients. The presence of FVIII inhibitors was quantified using an enzyme-linked immunosorbent assay, with a titer of &lt;0.28 ng/ml considered negative. Patients were divided into two groups: 59 with FVIII inhibitors (positive group) and 60 without inhibitors (negative group). The genotype of the subjects was determined using peripheral blood mononuclear cells and tetra-primer amplification refractory mutation system-polymerase chain reaction.&#x0D; RESULTS There was no association between IL-2 (rs2069762) gene polymorphism and FVIII inhibitor development on genotypes (p = 0.138) and allele frequencies (p = 0.780).&#x0D; CONCLUSIONS IL-2 (rs2069762) gene polymorphism is not a risk factor in the development of FVIII inhibitors in Indonesian patients with severe HA. Thus, further polymorphism studies in other cytokine genes are required to gain a comprehensive understanding of the FVIII inhibitor development.

The Association of Genetic Polymorphisms in Tumor Necrosis Factor-Alpha and Interleukins with Disease Severity or Response to Biological Therapy in Iraqi Rheumatoid Arthritis Patients: A Narrative Review

Background: Tumor necrosis factor-alpha (TNF-α) and interleukins play important roles in the pathogenesis of rheumatoid arthritis (RA). Genetic research has been employed to find many of the missing connections between genetic risk variations and causal genetic components. Objective: The goal of this study is to look at the genetic variations of TNF-α and interleukins in Iraqi RA patients and see how they relate to disease severity or response to biological therapy. Method: Using specific keywords, the authors conducted a systematic and comprehensive search to identify relevant Iraqi studies examining the genetic variations of TNF-α and interleukins in Iraqi RA patients and how they relate to disease severity or response to biological therapy. Results: Thirteen studies have looked at TNF-α and interleukin genetic polymorphisms in Iraqi RA patients. Only the IL-2, IL-4, IL-6, IL-17, and IL-23 receptor gene polymorphisms were explored for interleukins; however, the results of studies indicate no association between genetic polymorphism and the severity of RA. Very few researchers examine the correlation between genetic variation and TNF-α inhibitor responsiveness. Numerous studies have been conducted to investigate the genetic variations of the TNF-α promoter. The -308 G/A region in the promotor region was the most studied location.

The role of polymorphic loci of the cytokine gene IL6 (C174G) in inflammatory and ulcerative lesions of the stomach

Purpose of the study. To study the distribution and role of polymorphic loci of the cytokine gene IL6 (C174G) in inflammatory and ulcerative lesions of the stomach. Material and research methods. In this study, the detection of the polymorphic IL6 gene (C174G) was carried out in patients with inflammatory and ulcerative lesions of the stomach (n=96) and healthy individuals (n=88). Results. Analysis of the features of the distribution of IL6 (C174G) gene polymorphism among the studied groups of patients with inflammatory and ulcerative diseases compared with healthy ones, its contribution to the pathogenetic mechanisms of their formation was found, which is confirmed by the presence of a pronounced tendency to increase the frequencies of the major C allele by 3.3 times (χ 2 = 3.3; P=0.1) and C/C genotype by 2.9 times (χ 2 =2.9; P=0.1) in chronic non-atrophic gastritis (CNG), as well as the minor allele G by 2.5 times (χ 2 =2.5; P=0.2) in ulcerative diseases of the stomach (GU). In addition, the contribution of the studied genetic marker is also confirmed by the presence of a tendency to increase the major allele C by 3.1 times (χ 2 =1.9; P=0.2) and the C/C genotype by 2.8 times (χ 2 =1.4; P=0.3; OR=2.8; 95%CI: 0.52-15.37) among patients with CNG compared with those in the group with chronic erosive gastritis (CEG), as well as a statistically significant increase in these indicators by 5.8 times (χ 2 =6.6; P=0.025) and 6.2 times (χ 2 = 6.3; P=0.025), respectively, in comparison with the group of patients with GU. No significant association between the likelihood of erosive chronic gastritis and C174G polymorphic loci of the IL6 gene was found compared to healthy individuals. However, compared with GU, the contribution of the major C allele and the major C/C genotype is confirmed by the presence of a trend towards their increase among patients with CEG by 1.9 (χ 2 =2.0; P=0.2) and 2.2 times (χ 2 =2.1; P=0.2). Conclusions: based on the results of the study, it can be argued that the C174G polymorphic loci of the IL6 gene play a significant role in the mechanisms of formation of inflammatory and ulcerative diseases of the stomach in Uzbekistan.

The Effect of IL-6 174G > C Gene Polymorphism on Gastrointestinal Cancer: a Systematic Review and Meta-analysis.

IL-6 gene polymorphisms can play a role in the development or control of cancer by affecting cytokines. Gastrointestinal cancer is one of the most common types of cancer worldwide. The aim of this study was to investigate the effect of polymorphism of the IL-6 174G > C gene on gastrointestinal cancers based on a systematic review and meta-analysis, including gastric, colorectal, and esophageal cancer. In this study, a systematic and meta-analytical review of the study data on the effect of polymorphism of IL-6 174G > C gene on gastrointestinal cancer (gastric, colorectal, and esophageal cancer) in Scopus, EMBASE, Web of Science, PubMed, and Science Direct Databases was extracted without any time limit until April 2020. In order to perform the analysis of eligible studies, the model of random effects was used and the heterogeneity of studies was investigated with I2 index. Data analysis was performed with Comprehensive Meta-Analysis software (Version 2). The total number of surveyed studies in patients with colorectal cancer was 22 studies. Based on the results of meta-analysis, the odds ratio of GG genotype in patients with colorectal cancer was 0.88. The odds ratio of GC genotype obtained in patients with colorectal cancer was 0.88 and the odds ratio of CC genotype in patients with colorectal cancer was 0.92. The total number of surveyed studies in patients with gastric cancer was 12. Based on the meta-analysis results, the odds ratio of GG genotype in patients with gastric cancer was 0.74, the odds ratio of GC genotype in patients with gastric cancer was 1.27, and the odds ratio of CC genotype in patients with gastric cancer was 0.78. The total number of surveyed studies in esophageal cancer patients was 3 studies. Based on the results of meta-analysis, the odds ratio of GG genotype in patients with esophageal cancer was 0.57, the odds ratio of GC genotype in patients with esophageal cancer was 0.44, and the odds ratio of chance of CC genotype in patients with esophageal cancer was 0.99. In general, different genotypes of polymorphism of the IL-6 174G > C gene reduce the risk of gastric, colorectal, and esophageal cancer. However, the GC genotype of this gene was associated with a 27% increased risk of gastric cancer.

Relationship between IL-17, TNF-α, IL-10, IFN-γ, and IL-18 polymorphisms with the outcome of hepatitis B virus infection in the Turkish population.

Hepatitis B virus is a global threat that can lead to liver cirrhosis and hepatocellular carcinoma. For the treatment of chronic hepatitis B virus, polymorphisms might be an option for gene treatments. This study aimed to investigate the effects of IL-17, TNF-α, IL-10, IFN-γ, and IL-18 gene polymorphisms on hepatitis B virus infection in the Turkish population. The genotypes and allele distribution of 75 patients exposed to hepatitis B virus and 50 healthy control individuals were analyzed. The real-time polymerase chain reaction method was used for identification. A correlation was observed between susceptibility to hepatitis B virus infection and IL-17 Exon 3/3'UTR (rs1974226) C, IL-17 Exon 3 (rs763780) A, IL-18 (-607) (rs1946518) A alleles, and IL-17 Exon 3 (rs763780) AA genotype (p=0.006, p=0.009, p=0.025, and p=0.008, respectively). Furthermore, IL-18 (-137) (rs187238) TT genotype and TNF-α-308 (rs1800629) G and A alleles, were associated with protection against hepatitis B virus infection (p=0.0351 and p=0.032, respectively). This study demonstrated that TNF-α (-308), IL-17 (Exon 3/3' UTR), IL-17 (Exon 3), and IL-18 (-607) polymorphisms are associated with hepatitis B virus infection. Therefore, these may serve as potential therapeutic targets for chronic viral hepatitis in the Turkish population.

ПРОГНОСТИЧЕСКАЯ ВОЗМОЖНОСТЬ ИММУНОГЕНЕТИЧЕСКИХ ИССЛЕДОВАНИЙ В ИЗУЧЕНИИ ЗАБОЛЕВАЕМОСТИ МОЧЕКАМЕННОЙ БОЛЕЗНЬЮ У ДЕТЕЙ

Objective: To determine the genetic polymorphism associated with the development of urolithiasis (UL) in children of the Uzbek population. Methods: The study was conducted in the Specialized Children's Surgical Hospital of the Samarkand State Medical University between 2012 and 2019. In the first stage, a retrospective analysis of the case histories of 652 admitted patients was undertaken. In the second stage, 200 children aged 1 to 17 years were enrolled in the study, of which 100 were diagnosed with UL (main group), and 100 comprised the control group without UL (hospitalized for minor planned surgical interventions, such as circumcision or hernia repair). Immunogenetic studies of the vitamin D receptor (VDR), IL-1β, and IL-18 genes were carried out. Results: The obtained results indicate that polymorphism of the VDR and IL-1β genes plays an important role in susceptibility to UL. In the study groups, a statistically significant association of F/f+f/f genotypes of the VDR gene (Fok-1) with UL was found, which was 1.3 times more frequent in the main group than in the control one (p=0.033; χ2 =4.56). The C/C allele of the IL-1β gene was significantly more frequently detected in the main vs. control group (p=0.027; χ2 =7.23; df=2). The distribution of frequency of IL-18 (+105A/C) gene polymorphism for all models of inheritance was not statistically significantly different in the main and control groups (p&gt;0.05; χ2 =3.93; df=2). Conclusion: : The role of the immunogenetic method in the detection of susceptibility to UL development was determined in the study of the distribution of polymorphic markers of the VDR and IL-1β genes, indicating the significance of the immunogenetic factors for the predisposition to UL in children of the Uzbek population which may predict the disease at its preclinical stage. Therefore, in the interests of the early diagnosis of UL in children of the Uzbek population, it is reasonable to include testing for FokI genotype and polymorphism of VDR and IL-1β genes in the complex program of examination.

Gene polymorphisms of interleukin 10 (− 819 C/T and − 1082 G/A) in women with ovarian cancer

BackgroundOvarian cancer (OC) is the leading cause of death associated with gynecologic cancer. IL-10 plays an important role in tumorigenesis. We investigated IL-10 gene polymorphisms in OC patients. The current case–control study screened forty-eight women with OC and forty-eight healthy women who did not have OC. The genotyping of SNPs (− 1082 G > A; rs1800896 and − 819 C > T; rs1800871) of the IL-10 gene was done by tetra primers sequence-specific primer polymerase chain reaction (SSP-PCR) technique. The plasma levels of IL-10 were measured using an enzyme-linked immunosorbent assay (ELISA).ResultsFor IL-10 (− 1082 G/A) polymorphism, the G (wild allele) was significantly associated with increasing the risk of OC (OR = 2.054 with CI = 1.154–3.657; P < 0.05), while the A (variant allele) and AA genotype was significantly associated with decreasing the risk of OC (OR = 0.487 with CI = 0.273–0.867; P < 0.05) and (OR = 0.15; 95% CI = 0.04–0.63; P < 0.05), respectively. For IL-10 (− 819C/T) polymorphisms, the T allele (variant allele) and (TT, CT genotypes) were significantly associated with increasing the risk of OC (OR = 2.800 with 95% CI = 1.577–5.037; P < 0.05), (OR = 18.33 with 95% CI = 3.46–97.20; P < 0.001), and (OR = 9.44 with 95% CI = 2.52–35.40; P < 0.001), respectively, while the C (wild allele) was significantly associated with decreasing the risk of OC (OR = 0.357 with 95% CI = 0.199–0.642; P < 0.05). The haplotype analysis for (− 1082 G > A and − 819 C > T shows the GT haplotype was significantly associated with increasing the risk of OC (OR = 50.09 with CI = 6.34–395.92; P < 0.001). OC was substantially correlated with IL-10 level (r = 0.457; p < 0.001). There is no linkage disequilibrium (LD) between IL 10 − 1082 G/A and IL 10 − 819 C/T (D′ = 0.1315, r2 = 0.016; P = NS). A statistically significant positive relationship existed between IL-10 and CA125 and ALT (P < 0.05). IL-10 and albumin showed a strong negative association (P < 0.05), whereas the correlation of IL10 plasma level with BUN, AST, T. Bil., TLC, PLT, Cr., and HB has not any significant value (P > 0.05).ConclusionsOverall, this study supports an association of IL-10 (− 1082 G/A and − 819C/T) polymorphisms with the risk of ovarian cancer.

Association between IL-1 Gene Polymorphisms and Stage III Grade B Periodontitis in Polish Population

Periodontitis is a chronic multifactorial inflammatory disease originating from microbial, environmental and genetic factors. The present study aimed to find an association of genetic polymorphisms at IL-1A-889 and IL-1B+3953 loci in Polish patients with stage III grade B periodontitis and periodontally healthy subjects. Fifty patients with stage III grade B periodontitis (tests) and thirty-five periodontally healthy controls were included in the study. To determine IL-1A and IL-1B gene polymorphisms, buccal swab-derived DNA obtained by means of the GenoType PST test was used. There were no statistically significant differences regarding the prevalence of IL-1A-889 or IL-1B+3953 alleles between groups. The frequencies of different IL-1A-889 genotypes did not differ significantly between groups. The IL-1B+3953 C/T genotype was significantly more predominant in periodontitis patients than in controls, whereas C/C genotype prevalence was significantly lower in the test group. Complex genotypes consisting of at least one IL-1A-889 and IL-1B+3953 T allele occurred significantly more frequently in subjects with periodontitis. Stage III grade B periodontitis may be associated with the IL-1B+3953 T allele and composite IL-1 polymorphism. Reduced susceptibility to periodontal disease was present in IL-1A-889 and IL-1B+3953 C/C homozygotic patients.