Interleukin-10 Polymorphisms Research Articles

Association of interleukin polymorphisms and inflammatory markers with hospitalization, survival, and COVID-19 severity in type 1 diabetes patients: A multivariate and Cox regression analysis.

This study investigates the association between interleukin polymorphisms (IL-6, IL-10, IL-12A, and IL-18), inflammatory markers, and COVID-19 severity in Type 1 diabetes (T1D) patients. A prospective observational study enrolled 80 female T1D patients hospitalized with COVID-19 and a control group of 30 females without COVID-19. Significantly higher cytokine levels were observed in COVID-19 patients (IL-6: 64.1 ± 30.1 pg/mL, IL-10: 11.7 ± 5.8 pg/mL, IL-12A: 6.7 ± 2.9 pg/mL, IL-18: 195.4 ± 60.7 pg/mL) compared to controls (all p < 0.001). Genotype analysis revealed that the IL-6 GG and IL-18 TG genotypes were associated with elevated cytokine levels, prolonged hospitalization, and increased mortality risk (hazard ratios [HR]: IL-6 GG: 1.25, IL-18 TG: 1.30). ROC analysis indicated IL-18 (AUC: 0.88) and IL-6 (AUC: 0.84) as strong predictors of hospitalization. Cox regression showed that IL-6 and IL-18 levels significantly affected hospitalization duration and survival, while IL-12A displayed a protective effect (HR: 0.92). Kaplan-Meier analysis confirmed shorter survival for the IL-6 GG and IL-18 TG genotypes, supporting the prognostic role of cytokine levels and genotypes in COVID-19 management. This study highlights the potential of interleukin polymorphisms as biomarkers for COVID-19 severity in T1D patients.

The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative Review.

Preterm labor is a leading cause of neonatal morbidity and mortality worldwide. Previous research has indicated that an inflammatory response or microbial invasion of the amniotic cavity is a pathological condition linked to preterm birth; hence, inflammatory markers such as metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and interleukin-8 (IL-8) have been utilized to predict preterm delivery. The identification of reliable biomarkers for early prediction is critical for improving maternal, fetal, and neonatal outcomes. To address this issue, a literature review has been conducted on PubMed/Medline and Scopus databases for articles investigating the possible correlation between IL6, IL8, and MMP9 and preterm labor. Using a comprehensive search of the PubMed and Scopus databases, 12 studies were analyzed to identify the correlation between these biomarkers and preterm labor. Seven studies point the impact of increased IL-6 levels or polymorphisms of the gene and higher incidence of preterm labor. Two of the included studies identified the increased risk for preterm birth in elevated levels of IL-8 in amniotic fluid. Six studies highlight the increased incidence of preterm birth in women with polymorphisms of the MMP-9 gene. Elevated IL-6 levels and specific gene polymorphisms are strongly associated with preterm delivery risk, with IL-8 concentrations correlating with systemic inflammation and histologic chorioamnionitis. MMP-9 gene variations and protein levels showed significant predictive value for membrane rupture and labor onset. The findings emphasize integrating these biomarkers into diagnostic tools for routine prenatal care, enhancing early detection, risk stratification, and timely interventions to improve maternal and neonatal outcomes.

IL-10 EXPRESSION LEVELS AS POTENTIAL BIOMARKER IN WOMEN WITH SLE

Systemic Lupus Erythematosus (SLE) is a multi-systemic autoimmune disease. Its etiology is unclear; however, genetics, environmental, and immunological factors have already been related to the pathogenesis of the disease. There is evidence that cytokines can contribute to SLE, modulating innate and adaptive immune responses. Interleukin-10 (IL-10) is a pleiotropic cytokine previously related to SLE patients and disease activity status. Genetic polymorphisms at the promoter region of IL-10 have been associated with differential protein production, but the findings are conflicting. To assess the potential involvement of polymorphisms -1082 A/G (rs1800896) and -819 A/C (rs1800871) on the susceptibility to disease and clinical features, we identified these variants by TaqMan® SNP assay in a sample of 135 SLE cases and 130 matched controls from an admixed Brazilian population. High IL-10 expression genotypes (-1082 AG or GG) were associated with a protection for SLE (OR 0.317; 95% CI 0.189–0.525; p = 0.001), while no significant results were found for -819 A/C (OR 1.907; 95% CI 0.966–3.921; p = 0.063). Haplotypes of medium or high IL-10 expression were associated with anti-RO positive autoantibodies (p = 0.038), early diagnosis (p = 0.022), and longer fertility time (p = 0.019), possibly predicting a premature but milder disease. These findings indicate that IL-10 polymorphisms influence the susceptibility to SLE in this Brazilian South population and could predict a phenotype characterized by positivity to Anti-RO, premature diagnosis, and longer fertility time.

Association of genetic variations of interleukin-6 polymorphism (rs1800795) with susceptibility to Hashimoto’s thyroiditis in West Algerian population

Aim: Hashimoto’s thyroiditis is a polygenic auto-immune disease with a complex etiopathogenesis. It is more common in females. An imbalance between pro-inflammatory and anti-inflammatory cytokines may play an important role in the disease pathogenesis. Numerous studies have been conducted to find an association between genetic polymorphisms and the development of Hashimoto’s thyroiditis. In this context, we proposed to study the impact of the interleukin-6 (IL-6) gene polymorphism (rs1800795) on the genetic susceptibility to Hashimoto’s thyroiditis. Methods: Polymorphism in IL-6 gene (rs1800795) was assessed in a case-control study involving a population of Western Algeria with 81 Hashimoto’s thyroiditis patients and 211 unrelated healthy subjects, matched in age and sex. The DNA was extracted by a magnetic bead-based technique. The genetic study was performed by molecular biology: real-time PCR using TaqMan single nucleotide polymorphism (SNP) genotyping assay with Applied Biosystems 7500 device. Results: Results showed that the GG and GC genotypic distribution is similar between patient and control groups with a higher frequency of the GG genotype (80.25% in patients and 78.67% in controls vs. 19.75% of patients and 20.38% of controls with the GC genotype). The CC genotype is absent in patients and present in only 02/211 healthy subjects. The frequency of the polymorphic G allele was similar in the two groups, with 90.1% and 88.8% in patients and controls respectively (P &gt; 0.05). Conclusions: This study reports no significant difference in IL-6 (-174 G/C) gene polymorphism at the allelic or the genotypic level between Hashimoto’s patients and the control group (P &gt; 0.05). No association between the SNP IL-6 rs1800795 and susceptibility to Hashimoto’s thyroiditis in Western Algerian population.

Effect of novel IL-8 gene mutation on its protein structure and stability among ovarian cancer patients in Saudi Arabia

Despite advancements in therapeutics, early diagnosis of ovarian cancer (OC) remains a challenge due to its asymptomatic progression and it is often diagnosed at an advanced stage. Interleukin-8 (IL-8), a pro-inflammatory chemokine with angiogenic activity, plays a pivotal role in inflammation and carcinogenesis. Therefore, it is of interest to investigate the association between IL-8 polymorphisms and OC risk. A novel non-synonymous SNP (nsSNP, c.193G&gt;A; p.Glu65Leu) was identified in exon 2 of the IL-8 gene in 5 patients, 3 with stage III and 2 with stage II tumor. Structural analysis suggested that the p.Glu65Leu mutation alters the IL 8 protein conformation showing functional impairment. Thus, data shows that IL-8 c.193 G&gt;A (Glu65Leu) polymorphism may contribute to tumor susceptibility. However, further studies are warranted to understand the role of IL-8 polymorphism in OC.

A Meta-Analysis of Association Between Interleukin Polymorphisms (rs4073, rs1800925, rs1179251, rs1179246, rs2227485, rs17855750, and rs153109) and Colorectal Cancer Risk.

Interleukins (ILs) play a significant role in triggering the inflammatory response in blood vessels and immune cells. A systematic review and meta-analysis were conducted to investigate the relationship between IL-8 (rs4073), IL-13 (rs1800925), IL-22 (rs1179251, rs1179246, and rs2227485), and IL-27 (rs17855750 and rs153109) polymorphisms and the risk of developing colorectal cancer (CRC). Four databases were searched up until October 13, 2023, without any restrictions, to find relevant studies. The association was evaluated using crude odds ratios (ORs) and 95% confidence intervals in five genetic models. A total of twenty-three articles were entered into the meta-analysis. The pooled ORs (p-values) for the IL-8 (rs4073) polymorphism were 0.98 (0.63), 0.93 (0.44), 0.89 (0.13), 0.94 (0.38), and 0.99 (0.90) for studies following HWE without heterogeneity, and for all studies with high heterogeneity were 1.03 (0.69), 1.30 (0.07), 1.04 (0.71), 1.12 (0.20), and 1.23 (0.06). For the IL-13 (rs1800925) polymorphism, the pooled ORs were 1.44 (0.06), 2.58 (0.0004), 1.72 (0.16), 1.82 (0.09), and 2.37 (0.001) in AHHDR models, respectively. The pooled ORs of IL-22 (rs1179251) polymorphism for AHHDR models were 0.97 (0.92), 0.92 (0.90), 0.98 (p = 0.95), 1.08 (0.87), and 0.96 (0.82), respectively. The pooled ORs of IL-22 (rs1179246) polymorphism for AHHDR models were 0.98 (0.67), 0.97 (0.80), 0.92 (0.36), 0.93 (0.42), and 1.02 (0.84), respectively. The pooled ORs of IL-22 (rs2227485) polymorphism for AHHDR models were 1.47 (0.02), 2.03 (0.02), 1.28 (0.29), 1.52 (0.06), and 1.70 (0.04), respectively. The pooled ORs of IL-27 (rs17855750) polymorphism for AHHDR models were 0.53 (0.46), 0.19 (0.28), 1.10 (0.60), 0.55 (0.58), and 0.27 (p = 0.05), respectively. The pooled ORs of IL-27 (rs153109) polymorphism for AHHDR models were 1.28 (0.007), 1.45 (0.002), 1.40 (0.0002), 1.41 (< 0.0001), and 1.20 (0.09), respectively. The results reported that just the TT genotype of IL-13 (rs1800925), the T allele and TT genotype of IL-22 (rs2227485), and the G allele and GG, AG and GG + AG genotypes of IL-27 (rs153109) polymorphisms had an elevated risk in CRC patients.

Associations Between Interleukin-10 Polymorphisms and Susceptibility to Sjögren's Syndrome: A Meta-Analysis.

This study sought to investigate the association between interleukin-10 (IL10) polymorphisms and susceptibility to Sjögren's syndrome. A systematic search of the Medline, Embase and Web of Science databases was conducted to identify relevant articles from inception to April 2024. No restrictions were placed on race, ethnicity or geographic area, but only studies published in English were included. A meta-analysis was conducted to evaluate the association among the IL10-1082 G/A (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms, as well as their haplotypes and the risk of developing Sjögren's syndrome. The included studies involved 998 Sjögren's syndrome patients and 1576 controls. Ten studies were included in the meta-analysis. Meta-analysis of the IL10-1082 G/A polymorphism revealed no significant association with Sjögren's syndrome (odds ratio [OR]=1.115, 95% confidence interval [CI]: 0.888-1.401, p=0.343), with stratification by ethnicity yielding consistent results for Europeans and Latin Americans. Similarly, the IL10-819 C/T polymorphism was not associated with Sjögren's syndrome in any study subjects (OR=0.859, 95% CI: 0.648-1.138, p=0.290). The IL10-592 C allele also exhibited no association with Sjögren's syndrome (OR=1.131, 95% CI: 0.776-1.646, p=0.522). However, the GCC carrier status demonstrated a significant association with Sjögren's syndrome across all study subjects (OR=1.496, 95% CI: 1.200-1.865, p<0.001), particularly in Europeans (OR=1.444, 95% CI: 1.085-1.921, p=0.012) and Latin Americans (OR=1.324, 95% CI: 1.115-2.366, p=0.012). A significant protective effect of the homozygous ATA/ATA haplotype on Sjögren's syndrome was found in Europeans (OR=0.320, 95% CI: 0.121-0.846, p=0.022). This meta-analysis indicates a significant link between carrying the GCC haplotype of the IL10-1082 G/A, -819 C/T and -592 C/A polymorphisms and an increased susceptibility to Sjögren's syndrome. Conversely, the homozygous ATA/ATA haplotype appears to confer protection against the risk of Sjögren's syndrome, particularly in European populations.

IL-6 (rs1800797) Variant as an Immunomarker for Children's Adenovirus Respiratory Infection: A Prospective Insight

Background: One important cytokine that modulates the immune response during infections is IL-6. Gaining knowledge about the correlation between IL-6 genetic variants and susceptibility to disease can be quite beneficial in understanding the pathophysiology of various illnesses. Objective: Present study aims to explore the relationship between the polymorphisms IL-6-174 G/C and IL-6-597 A/G and their potential role in disease susceptibility and progression. Methods: A 210 adenovirus respiratory patients at Baghdad Hospital. Patients with comorbidities or previous respiratory infections were excluded. Nasopharyngeal swabs were collected and tested for adenovirus using PCR. From the specimen, genomic DNA was isolated. Genotyping PCR-RFLP was used to genotype the Interleukin-6 (-597 A/G, rs 1800797) polymorphism. Results: Interlukin-6-174 G/C polymorphism and illness sensibility are strongly correlated, according to the study's findings. More precisely, it was found that both a worse development and a race probability of contracting a severe COVID-19 infection were analogous with the IL-6-174 G/C polymorphism. In addition, it was linked to the periodontitis probability. Discussion: Current studied results point to the potential importance of the IL-6-174 G/C polymorphism in disease vulnerability, especially in cases of acute COVID-19 infection and periodontitis. However, as there is no proof of a strong association between the IL-6-597 A/G polymorphism and type 2 diabetes or malignant tumors, its significance in detected disease susceptibility remains unclear. Conclusion: Our study highlights the potential role of IL-6 genetic variations, including IL-6-174 G/C, in the development and vulnerability of illness. To understand how these genetic polymorphisms affect the course of disease and their molecular relationship, more research is required.

Significant association between insulin-like growth factor 2 mRNA-binding protein 2, interleukin-6 polymorphisms, and type 2 diabetes mellitus

Background: The study aimed to detect the association between insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and interleukin-6 (IL-6) polymorphisms among type 2 diabetes mellitus (T2DM). Materials and Methods: This study involved 500 individuals; 250 obese DM cases and 250 healthy controls. The polymerase chain reaction restriction fragment length polymorphism was used to identify the genotype of the IGF2BP2 gene for the small nucleoproteins rs4402960 (G&gt;T) and small nucleoproteins rs800795 (G&gt;C). Results: The results indicated that the mutant C-allele of the single nucleotide polymorphism (SNP) rs1800795 variant was highly significantly associated with the study group (P = 0.002). The occurrence of genotypes (C/G and C/C) versus normal G/G genotype of the IL-6 variant was highly significant (P = 0.004) in the study group (49.2% vs. 50.8%) compared to the control group (62% vs. 38%). Similar findings were observed in SNPs for the rs440960 variant, in which the T-allele indicated a highly significant relationship (P = 0.0001) with the study group; the frequency of G/G genotype versus both (T/T and G/T) genotypes was highly significant (P = 0.0001) in the case group (34% vs. 66%) than in the healthy control group (52% vs. 48%). Conclusion: The current study indicated that IGF2BP2 rs4402960 and IL-6 rs1800795 polymorphism were highly significantly associated with the increased risk of obese T2DM among the Saudi Arabian population and presented a genetic model to screen the high-risk individuals with further validations.

Meta-analysis of interleukin-10gene polymorphisms and tuberculosis susceptibility: Insights from recent studies.

Tuberculosis (TB) remains a universal health problem with significant morbidity and mortality. Understanding the genetic factors affecting TB susceptibility is crucial for effective prevention and treatment. Interleukin-10 (IL-10), a regulatory cytokine, may influence TB pathogenesis through genetic variations. The PubMed, Embase, and Google Scholar databases were searched to find studies on the relationship between IL-10gene variants and tuberculosis. Relevant studies from 2016 to 2024 were identified through database searches. The selected case-control studies met the inclusion criteria. Software such as Review Manager was used to analyze quantitative data, with statistical significance set at p< 0.05. We calculated odds ratios and their respective confidence intervals to evaluate the associations. Nine studies examined IL-10 gene polymorphisms (rs1800871 and rs1800872) in TB susceptibility. The present study did not show a notable association between IL-10 gene polymorphisms and TB among all genetic models (allelic, homozygote, heterozygote, dominant, and recessive). The obtained p-value > 0.05 indicates an insignificant association between both gene polymorphisms of IL-10. An OR-1.13; 95% CI-0.85, 1.50 was obtained for the SNP rs1800871, whereas an OR-1.02; 95% CI-0.75, 1.40 was obtained for the SNP rs1800872. Our meta-analysis revealed no significant association between IL-10 gene polymorphisms and TB susceptibility, suggesting that these variations may not significantly contribute to TB susceptibility. Further research with a larger sample size and diverse ethnicities is needed to explore additional genetic variations and their implications in TB pathogenesis.

Clinical Significance of IL-6 Gene Polymorphism on Erythropoietin Responsiveness in Hemodialysis Patients

Abstract Background The plasma levels of the cytokine interleukin-6 (IL-6) have been reported to be associated with risk of chronic kidney disease (CKD) and erythropoietin (EPO) responsiveness. The G/C promoter polymorphism of IL-6 is associated with expression and levels of IL-6, so it may confer increased risk to CKD and modulate EPO responsiveness. Aim of the Work This study aims to evaluate the frequency of 174G/C IL-6 gene promoter polymorphism in hemodialysis (HD) patients and to assess the impact of this allelic variation on erythropoietin (EPO) responsiveness. Patients and Methods This study was conducted on fifty Chronic Kidney Disease (CKD) patients undergoing hemodialysis (HD) recruited from Nephrology Medicine Department at Ain Shams University hospitals, and ten healthy age and sex matched controls. All patients received recombinant human erythropoeitin (rHu-Epo) regimens for treatment of anemia. All the patients were subjected to full history taking, basic laboratory investigations (CBC, Iron profile and kidney function tests) as well as determination of IL-6 rs1800795 (-174 G/C) gene polymorphism using Real time-polymerase chain reaction technique (RT-PCR). The patient’s group was further classified into two subgroups according to Hb level in response to erythropoietin stimulating agents (ESAs) in accordance with the European Best Practice Guidelines, in which responders have a Hb level ≥11 g/dl, and ESA non-responders have a Hb level&amp;lt;11 g/dl. The Erythropoietin resistance index (ERI) was calculated for all patients, with a median (IQR) of 16.5 (14.31 - 19.96). Accordingly all patients were further classified into tertiles according to the ERI. The higher tertile group is classified as more hypo-responsive/resistant. Results In the present study, The IL-6 -174 G/G genotype was the most common among the cases group. Seventy four percent of the patients had the wild GG genotype and 24% had heterozygous GC genotype while only 2% had the homozygous CC genotype. In the control group the G/G genotype was detected in (80%) of subjects followed by G/C genotype (20%). No statistically significant difference was observed between the control and cases group regarding the IL-6 genotype frequencies. Only eight out of fifty (16%) patients reached the target Hb, 4 of them (50%) had the GG genotype and the other 4 (50%) had the GC genotype. The non-responders genotypes were distributed as 78.6% GG genotype, 19% GC genotype and 2.4% with CC genotype. There was no statistical significant difference regarding the genotype frequencies of IL-6 gene polymorphism between the two groups. Similarly no statistically significant association was found between the IL-6 gene genotypes and the ERI tertiles. Conclusion IL-6 -174 G/C gene polymorphism was not found to be associated with EPO hypo-responsiveness in CKD patients in the studied group nor with the increased Erythropoeitin resistance index (ERI) values among them.

Effectiveness of zero dose HBV vaccine on prevention of HBV breakthrough infection among vaccinated Egyptian children

Hepatitis B virus (HBV) is a vaccine preventable disease. Sufficient post vaccination response is critical step to achieve infection eradication. Vaccine hypo-responsiveness is a major risk factor for HBV chronic infection. We aimed to evaluate the effectiveness of birth dose HBV vaccine in preventing perinatal HBV infection and to detect the rate of HBV surface antibody (HBs-Ab) seroconversion and its relation to interleukin-4 polymorphism (IL-4 PM) among a group of vaccinated Egyptian infants. This observational analytical study involved 77 infants aged 6 to 12 months who received 4 doses of HBV vaccine including a zero dose. We measured serum levels of HBV-DNA and hepatitis B surface antigen (HBsAg) as markers of infectivity, and the level of (HBsAb) to assess vaccine responsiveness. Cytokine gene analysis to detect IL-4 gene polymorphism and its association with vaccine un-responsiveness were investigated. We observed that none of the vaccinated infants acquired HBV infection. Of the included 77 infants, seroconversion against HBV was detected in 72 (93.5%), 28 (36.4%) had low response and 44 (57.1%) had high response. While 5 (6.5%) were non responders. There was significant association between IL-4 gene polymorphism and the poor seroconversion after HBV vaccination. (p=0.03). Furthermore, HBsAb titer was significantly lower in children who have IL-4 gene polymorphism (p=0.014). In conclusion, implementation of birth-dose HBV vaccination is effective for prevention of perinatal infection, but seroconversion rate may be insufficient to induce long term protection. IL-4 gene polymorphism is associated with poor response to HBV vaccine.

Interleukin-6 Receptor Gene rs1800795 Polymorphism and Expression of Interleukin-6 in Gingival Tissue in Patients with Periodontitis.

Periodontitis is a multifactorial inflammatory disease. This chronic periodontal disease is caused by a bacterial infection in the gums, which triggers a host inflammatory response. To eliminate the bacterial infection, immune response mechanisms are activated, leading to inflammation and damage to the periodontal tissues. This process involves many cytokines, including IL-6, a cytokine with antibacterial properties. An ongoing bacterial infection in the periodontal tissues leads to its excessive production, which increases inflammation. In this study, we examined IL-6 receptor gene rs1800795 polymorphism in patients with periodontitis in comparison with healthy subjects, as well as the correlation between rs1800795 genotypes and clinical parameters. Additionally we examined the expression of IL-6 in gingival tissue in patients with periodontitis and control subjects, as well as the correlation between gingival expression of IL-6 and clinical parameters. This study included 200 patients with periodontitis and 158 healthy subjects as the control group. Biopsy specimens of gingival tissue in which IL-6 expression was detected were taken from 14 patients with periodontitis and 8 controls who had undergone minor surgery. There were no statistically significant differences in the distribution of IL-6 rs1800795 genotypes and alleles between patients with periodontitis and control subjects. There were also no statistically significant correlations between IL-6 rs1800795 genotypes and clinical parameters in patients with periodontitis. There were no differences in IL-6 expression in the gingival tissue between patients with periodontitis and controls. There was also no correlation between IL-6 expression in the gingival tissue of patients with periodontitis and clinical parameters. In the control group, IL-6 expression in gingival tissue correlated negatively with the approximal plaque index, which reflects the size of bacterial plaques. The results of our study suggest a protective role for IL-6 against bacterial growth in the periodontal tissue. However, it should be noted that several parameters directly or indirectly affect the accumulation of bacterial plaque.

Relationship Between IL-10 Single Nucleotide Polymorphisms (rs1800871, rs1800872, and rs1800896) and the Severity of COVID-19.

Background: Interleukin-10 (IL-10) is an anti-inflammatory cytokine whose levels are elevated in patients with severe COVID-19. IL-10 polymorphisms may play a role in increasing IL-10 levels and the severity of COVID-19. This study aimed to investigate the relationship between IL-10 single nucleotide polymorphisms (SNPs) (rs1800896 [-1082 C < T], rs1800871 [-819 A > G], and rs1800872 [-592 T > G]) and the severity of COVID-19 in patients from Kermanshah Province, Iran. Methods: A total of 150 patients with mild COVID-19 (84 men and 66 women aged 40.1 ± 12.44 years) and 143 patients with severe COVID-19 (76 men and 67 women aged 61.04 ± 15.65 years) participated in this study. Blood samples were collected from the patients, DNA was extracted, and the genotype of each SNPs was determined using the polymerase chain reaction-restriction fragment length polymorphism method. Result: The results of this study did not show a significant relationship between the genotypes of the three studied SNPs and the severity of COVID-19 (p > 0.05). Conclusion: According to our findings, these SNPs were not associated with COVID-19 severity in patients in Kermanshah.

Pharmacogenetic analysis of interleukin-10 variants and tacrolimus metabolism in kidney transplant patients from Pakistani population.

End stage renal disease (ESRD) occurs when the kidneys are unable to filter the waste products and excessive fluids from the blood that results into the accumulation of toxins and fluid in the body. Tacrolimus is commonly used immunosuppressant while sirolimus and cyclosporin are rarely used drugs to stop solid organ transplant rejection. The host's immunological response following transplantation produces interleukin-10 (IL-10), which influences the varied CYP3A-dependent drug disposition of tacrolimus. The aim of this study was to determine the genetic polymorphisms of IL-10 (rs1800871, rs1800872 and rs1800896) gene associated with tacrolimus metabolism in kidney transplant patients from Lahore Punjab, Pakistan. The study collected blood samples of 103 healthy individuals and 137 kidney transplant patients as control and treatment groups, respectively. We employed Tetra ARMS PCR for the genotype analysis of extracted DNA. The alleles were called on 2% agarose gel. Moreover, the study utilized SPSS software to analyze statistical significance of polymorphism. It was found that genotypic frequencies of IL-10 (rs1800871), IL-10 (rs1800872), and IL-10 (rs1800896) were (TT: 66.4%; TC: 31.4%; CC: 2.2%), (AA: 27.7%; AC: 54%; CC: 18.2%), (AA: 64.2%; GA: 17.5%; GG: 18.3%), respectively among kidney transplant patients. All parameters show significant association at different points after transplantation. Genetic analysis showed that TC and CC genotypes in rs1800871 (OR (95%CI) = 5.721 (3.231-10.131), P < 0.001; OR (95%CI) = 3.370 (0.642-17.672), P = 0.150), AC and CC genotypes in rs1800872 (OR (95%CI) = 1.294 (0.695-2.410), P = 0.415; OR (95%CI) = 1.453 (0.671-3.147), P = 0.342), GA and GG genotypes in rs1800896 (OR (95%CI) = 42.952 (17.566-105.021), P = 0.001; OR (95%CI) = 7.040 (2.563-19.333), P = 0.342) was associated with risk of renal rejection in kidney transplant patients. Besides, genetic models showed that TT in rs1800871, AA genotypes in rs1800872 and rs1800892 were associated with risk of renal rejection under dominant model when compared to controls (OR (95%CI) = 5.721 (3.231-10.131), P < 0.001; OR (95%CI) = 1.335 (0.735-9.290), P < 0.341; OR (95%CI) = 24.629 (10.599-57.230), P < 0.001), respectively. From the results, it is concluded that genetic polymorphism of IL-10 (rs1800871, rs1800872 and rs1800896) has a highly significant association with risk of renal rejection in Pakistani kidney transplant patients.

Interleukin 18 (-137G/C, -607C/A) Polymorphisms as Genetic Biomarkers of Susceptibility to Systematic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology. Several studies have suggested that interleukin-18 (IL-18) is associated with SLE pathogenesis. The genotype distribution of IL-18 promoter polymorphisms differs among ethnic populations. The present study aimed to investigate the correlation between IL-18 polymorphisms at positions -137 and -607 in patients situated in Northeastern Iran. This case-control study examined the prevalence of IL-18 -137C/G and -607C/A polymorphic variants among 95 SLE patients referred to the Department of Rheumatology, who were referred to the general clinics of Ghaem Hospital and Imam Reza Hospital in Mashhad, Iran, were included in the study. In addition, 100 healthy individuals were included in the control group. DNA from whole blood was extracted by the salting-out method using a commercial kit (Biogene, US). Allelic and genotypic frequencies of polymorphisms (-137G/C, -607C/A) in the IL-18 promoter gene were analyzed using a polymerase chain reaction (PCR)-based amplification refractory mutation system (ARMS) method. The results of this study demonstrated that the frequency of SLE patients with the homozygous C/C genotype of the IL-18 promoter gene at position -137 was significantly higher than that of the homozygous G/G genotype (P < 0.001) in normal controls. Furthermore, the polymorphism analysis performed illustrated a significant association between (-137G/C) and (-607C/A) polymorphisms in the IL-18 promoter gene and SLE (P < 0.005). These results indicated that the 607A/A and 137C/C polymorphisms are more prevalent in SLE. Further research involving larger sample sizes from various populations is necessary to elucidate the role of these polymorphisms and the distribution of alleles in SLE patients.

Inflammatory Biomarkers in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Faction.

To verify the relationship between gene polymorphisms of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) with inflammation markers and codependent metabolic variables in patients with type 2 diabetes mellitus and chronic heart failure (CHF). This study included 154 patients (mean age, 69.1±3.2 years). The control group consisted of 47 patients with metabolic syndrome (MS) without CHF; the 2nd group included 56 patients with CHF with preserved ejection fraction (CHFpEF); and the 3rd group consisted of 51 patients with CHF with reduced ejection fraction (CHFrEF). The rs1800629 polymorphism of the TNF-α gene (TNF-α: G308A) was studied in real time by the polymerase chain reaction (PCR) method and the rs1800795 polymorphism of the IL-6 gene (IL-6: 174 G&gt;C) was studied by PCR with the electrophoretic detection. The frequencies of polymorphic alleles were compared with the clinical blood test results, plasma concentrations of C-reactive protein (CRP), TNF-α, leptin, and fibrinogen. Differences between the groups were determined using the F test. Relationships between individual studied parameters were identified using the regression analysis. In most patients, the occurrence of gene polymorphisms was eident as increased plasma concentrations of biomarkers. An association was found between the TNF-α gene polymorphism (G308A) and an increase in plasma TNF-α and between the IL-6 gene polymorphism (174 C&gt;G) and an increase in plasma CRP. In the CHFpEF group, the rs1800629 gene polymorphism was observed in 55% of patients, among whom 93% had increased TNF-α. The rs1800795 gene polymorphism was observed in 82% of CHFpEF patients, among whom 21% had increased CRP. In the CHFrEF group, the G308A transition in the TNF-α gene was observed in 53% of patients; an increase in the respective cytokine was noted in 67% of patients; the IL-6 gene polymorphism 174 C&gt;G was found in 78%, however, only 14% of patients with this polymorphism had also increased CRP. In the control group, the TNF-α G308A gene polymorphism was found in 30% of patients, while an increase in free TNF-α was associated with this polymorphism in 50% of patients; the IL-6 174 C&gt;G gene polymorphism was detected in 78%, while no increase in the CRP level was observed in this group. This demonstrates a high probability of the TNF-α G308A gene polymorphism occurrence in patients with CHF. Inflammatory markers are important predictors of CHF. The most significant predictor was the TNF-α G308A gene polymorphism, which was observed in more than 50% of patients, the majority of whom had an increase in plasma TNF-α.

Iraqi patients with a single-nucleotide polymorphism of interleukin-10 -1082G/A and interleukin-6 -174G/C susceptibility to asthma

The effects of genetic variations in the IL-10 -1082G/A gene and IL-6 -174G/C gene, as well as the genotypes and alleles linked to the prevalence of asthma disease, were investigated using a molecular and immunological study. Between October 2018 and the end of July 2020, 40 healthy individuals (20 females and 20 males) served as a control group for the study, which involved 50 asthmatic patients (31 females and 19 males) at the Allergy Centre, Al-Anbar Teaching Hospital, in Al-Anbar City. The study used the Single Specific Primer-Polymerase Chain Reaction (SSP-PCR) technique to show that the single nucleotide polymorphisms IL-10 -1082G/A and IL-6 -174G/C had a considerably high prevalence rate (P&lt;0.05) among asthma case and that there was an association between the polymorphism and the asthma risk. The findings indicate that asthma patients had considerably higher (P&lt;0.05) IL-10 A alleles and heterozygous GA genotypes (1082G/A) compared to the control group. Genetic variations affecting IL-10 production and the genotypes affecting IL-10 serum levels are associated with the occurrence of asthma and are attributed to the IL-10 -1082G/A promoter gene polymorphism. There was a strong correlation between cytokine levels, of disease development, and the genotypes of the AA and AG genes, indicating that IL-10 -1082A/G predisposition to asthma may be influenced by the gene promoter polymorphism. Asthma development and immunological markers (IL-10) are substantially correlated. One theory links allergic rhinitis to both the development of asthma and its risk. Inducing long-term immunological and clinical tolerance in patients was a good use of HDM immunotherapy. The current study's findings indicate a substantial difference between the asthma patients and the control group in terms of gene type and allele frequency of the IL-6 -174G/C polymorphism. The patients exhibited a higher prevalence of the G allele and the GG homozygous genotype than the control group. Therefore, it was shown that those with GG genotypes had a 2-fold increased probability of having asthma, indicating that patients were more prone to the condition.

The Influence of Genetics and Gene Polymorphism on Biological Complications for Dental Implant Survival: A Review.

The objective of this review is to expose the main genetic changes and genetic polymorphisms that may or may not be associated with greater susceptibility to reduced survival of dental implants and, consequently, to their loss. Case-control studies that fully portrayed the specific types of genetic polymorphisms that may be associated with dental implant failure were included by searching in the PubMed, Scopus, and Web of Science databases from 2010 to 2023. The following descriptors and their combinations in English were used to search for articles: "dental implants," "bone genes," "genetics," "polymorphism genetics," "genetic risk factor," and "interleukin." The initial search resulted in 107 results (PubMed n = 47, Scopus n = 14, and Web of Science n = 46). After a manual search, reviewing each article's title and abstract, and excluding duplicates, systematic reviews, and literature reviews, 30 articles were selected. After reading these 30 articles in full, 18 studies that did not describe the specific genetic polymorphism in relation to dental implant survival were excluded. Therefore, 12 articles were included in this review. The genetic polymorphisms of interleukin (IL)-1A, IL-1B, IL-4, IL-6, IL-10, IL-1 receptor antagonist, tumor necrosis factor-α, receptor activator of nuclear factor kappa B legend, and cluster of differentiation 14 were analyzed in the included studies. In seven of the studies, a statistically significant correlation between genetic polymorphisms and dental implant failure was observed. Of the polymorphisms studied, IL-1A (-899), IL-1B (+3954), and IL-4 (+33) showed a greater association with dental implant loss.

Assessment of Interleukin 10 (IL-10) Single Nucleotide Polymorphism (SNP) in Irritable Bowel Syndrome (IBS) Patients

Abstract Background Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder characterized by the presence of abdominal pain, bloating and altered bowel habits. The pathophysiological mechanisms underlying IBS are unclear. The abnormalities of motility, visceral hypersensitivity, gut microbial alteration and psychological stress contribute to the clinical symptoms of IBS. The associations of IBS and its risk gene polymorphisms have been ascertained by many researchers. Single nucleotide polymorphisms (SNPs) represent the most widespread type of sequence variations in genomes. It is known to be valuable genetic markers, because it may reveal the evolutionary history and common genetic polymorphisms that explain the hereditary risks for common diseases. Cytokines are involved in the pathogenesis of IBS. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphism (rs1800871) -819 position to IBS. Objective We assessed interleukin 10 (IL-10) single nucleotide polymorphism rs1800871 (-819 C/T) in IBS patients. Method This was comparative case - control study for 40 participants, 20 cases and 20 controls, IL-10 rs1800871 (−819 T/C) single nucleotide polymorphism (SNP) was done via real time polymerase chain reaction for both study groups to assess its relation with IBS. Results The studied participants were divided into two groups according to ROME IV _criteria. For the case group (n = 20), the mean age was 41.05 ± 17.45 years, with 50% being male and 50% being female. In the control group (n = 20), mean age was 39.80 ± 14.84 years, with 25% being male and 75% being female Compared to the controls subjects, the frequencies of the IL-10 -819 T/T genotype and T allele were observed to be overrepresented in patients with IBS (60%; odds ratio [OR] = 1.143; 95% confidence interval [CI]: (0.152 – 8.593) for the TT genotype; P = 0.897) and (72.5%; OR: 1.582; 95% CI: (0.615 – 4.066)for the T allele; P = 0.341, respectively). The results demonstrated that T/T genotype was the most common genotype in the case group (60%). T allele was the most prevalent in case group (72.5%), while the C allele was the least prevalent (27.5%). However, T/T polymorphism in cases was greater than in control with non- statistical significance (p = 0.157). Conclusion IL-10 polymorphism (rs-1800871) has no association with IBS, However, T/T genotype was shown frequently in cases, with strong association with IBS. Abbreviations: IBS (irritable bowel syndrome), IL-10 (Interleukin-10 cytokine), SNP (single nucleotide polymorphism)