IL-10 Single Nucleotide Polymorphisms Research Articles

Evaluation of IL-4 and IL-13 Single Nucleotide Polymorphisms and Their Association With Childhood Asthma and Its Severity: A Hospital-Based Case-Control Study.

Asthma is a common, chronic, atopic respiratory disease that is on the rise among children and adults worldwide. Various environmental, genetic, and biological interactions contribute to the surge in susceptibility to this disease. Interleukin (IL) genes, particularly IL-4 and IL-13, have been linked to asthma pathogenesis. The present study aims to investigate the genetic aberrations, specifically single nucleotide polymorphisms (SNPs) of IL-4 and IL-13, and their association with childhood asthma and its severity. An unmatched hospital-based case-control study was conducted in a tertiary care hospital in Assam, India. The sample size was calculated to be 120 (60 cases and 60 controls) using the Epi Info software version 7.2 (Centers for Disease Control and Prevention, Atlanta, GA, USA), assuming a confidence interval of 95%, a power of the study at 80%, a ratio of control to cases as 1, a proportion of controls with exposure at 22%, and a proportion of cases with exposure at 46%. A total of 53 clinically diagnosed cases of childhood asthma in the age range of three to 12 years and 39 healthy controls free from respiratory diseases and having no history of asthma and/or allergy of the same age group attending a tertiary care hospital were included in the study. Children who never had asthma or allergies and who did not suffer from any upper or lower respiratory infections for the previous four weeks were considered controls. Prior informed consent and ethical clearance were obtained. Very seriously ill cases and controls were excluded from the study. The genetic investigation used polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP), to discover SNPs in the IL-4 and IL-13 genes. Sequencing analysis was done for the cases with +2044 G>A of the IL-13 gene in relation to the severity of the disease. The difference in the proportions of specific SNPs between cases and controls was analyzed using the χ2test (a p-value of <0.05 was considered significant). Both the rs2070874 and rs2243250 polymorphisms of IL-4 showed no statistically significant associations. The mutation of the IL-13 gene in 1111C>T was higher among cases than controls. Both genotypic and allelic distributions of the +2044G>A polymorphism of the IL-13 gene revealed a significant association (p<0.05) with the severity of the disease. Genetic aberrations in SNPs of IL-4 and IL-13 are prevalent among the pediatric patients of the study region. The SNP +2044G>A of IL-13 is instrumental in disease manifestation and severity among the pediatric population of the study region.

Mother's smoking habits affects IL10 methylation but not asthma in Ecuadorian children.

To identify polymorphisms and methylation profiles in the IL10 gene associated with asthma in children aged 5 to 11. A case-control study was conducted with asthmatic and non-asthmatic children aged 5 to 11 years in Cuenca-Ecuador. Data on allergic diseases and risk factors were collected through a questionnaire for parents. Atopy was measured by skin prick test (SPT) to relevant aeroallergens. Three IL10 single nucleotide polymorphisms were evaluated in all participants, and methylation analysis was performed in 54 participants. Association between risk factors, allergic diseases and genetic factors were estimated using multivariate logistic regression. The results of polymorphisms showed no differences between cases and controls when comparing the SNPs rs3024495, rs3024496, rs1800896 allelic and genotypic frequencies. In the methylation analysis, no differences in the IL10 methylation profile were found between cases and controls; however, the multivariate analysis showed an association between the mother's smoking habits and the IL10 methylation profile. Smoking habit could be essential as an environmental exposure factor in regulating gene expression in children with asthma.

Association of Interleukin-12 and Interleukin-18 Polymorphisms with Acute Lymphoblastic Leukemia Disease in Iraqi Patients

Acute lymphoblastic leukemia (ALL) is a blood cancer where high numbers of abnormal, immature lymphocytes called blasts start over-multiplying in the bone marrow. The lymphocyte cells and interleukins are crucial for controlling the immune response in tumor microenvironment. Many of the single nucleotide polymorphisms (SNPs) of some interleukin genes may change protein synthesis or function and regulate the immune response. A lot of these changes have been connected to a high risk of developing cancer. Aim of this study was to investigate the potential association between IL-12 (+1188 A/C) (rs3212227) and IL-18 (–607 A/C) (rs1946518) polymorphism with serum levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) and their genotypes association with the susceptibility to ALL disease in Iraqi patients. The study included 59 ALL patients and 30 healthy controls. The detection of IL-12 and IL-18 SNP genes was determined by ARMS-PCR methods and serum levels of IFN-γ and TNF-α were determined by utilizing enzyme linked immuno-sorbent assay (ELISA) kits. Results observed no significant association of IL-12 and IL-18 polymorphism with serum IFN-γ and TNF-α level. Genotyping frequencies of IL-12 (+1188A/C) CA, AA and CA+AA genotypes showed a strong association with the development of ALL disease, IL-18 genotypes showed no significant association with the disease progression.

The linkage between IL-6 rs1800797 variant and breast cancer susceptibility in Bangladeshi women: A case-control study.

Breast cancer is one of the deadliest diseases affecting women in Bangladesh, and its prevalence is increasing year by year. Although several IL-6single nucleotide polymorphisms have been implicated in BC susceptibility and prognosis in various studies, no research has been done to investigate the relationship between breast cancer and IL-6in Bangladeshi women. This investigation aimed to explore the linkage between the rs1800797 variant of IL-6and the susceptibility to breast carcinoma among women in Bangladesh. The IL-6rs1800797 variant was genotyped in 218 subjects (110 cases and 108 controls) using the tetra-primer ARMS-PCRmethod. The statistical analysis was applied utilizing the SPSS software version 24.0. UALCAN database was used for IL-6 mRNA analysis, and genotype-based gene expression was retrieved from GTEx Portal. This study found a significant link between IL-6rs1800797 variants and increased chance of breast cancer across different genetic inheritance models, including additive model 1 (AGvs. GG: OR = 2.16, p = 0.035); dominant model (AG + AA vs. GG: OR = 2.26, p < 0.05); overdominant model (AGvs. GG + AA: OR = 2.08, p < 0.05); and allelic model (A vs. G: OR = 2.15, p < 0.05). However, an insignificant association of breast cancer was found in both additive model 2 (AAvs. GG: OR = 2.91, p > 0.05) and the recessive model (AAvs. GG + AG: OR = 2.52, p > 0.05). Under the analysis of the probability of false positive reports, no significant values were found in different models when the OR was 1.5, and the prior probability was 0.25. A significant relationship was found between the IL-6rs1800797 genetic variant and the risk of breast cancer. However, the findings of the study should be further investigated with a larger sample size to validate the correlation.

The Concentrations of Interleukin-6, Insulin, and Glucagon in the Context of Obesity and Type 2 Diabetes and Single Nucleotide Polymorphisms in IL6 and INS Genes.

Obesity and diabetes are a problem of modern medicine. Although the environmental factors contributing to the development of these diseases are widely known, research into genetic factors is still ongoing. At the same time, the role of inflammation in the pathophysiology of obesity and diabetes is increasingly emphasized. Therefore, the purpose of this study was to investigate the influence of two selected polymorphisms (rs1800795 and rs3842729) on the development of obesity and type 2 diabetes. In this study, 118 participants were examined, including a control group (nonobese and nondiabetic group), an obese group, and a diabetic group. Genotype analysis was performed using the PCR-RFLP method. It has been shown that in patients with the G/G genotype within the rs1800795 polymorphism (IL6), the chance of developing type 2 diabetes is several times lower compared to patients with the G/C and C/C genotypes. However, the rs3842729 polymorphism (INS) does not directly affect the risk of obesity or type 2 diabetes (T2D), although elevated insulin concentrations have been observed in obese and diabetic patients. These results confirm the impact of the rs1800795 polymorphism on the development of diabetes; however, this relationship is more complex and requires further research on other factors.

Multiple sclerosis susceptibility may be associated with the coding rs20541 (R130Q) IL-13 gene polymorphism in the Polish population

Some of the multiple autoimmune diseases have been already associated with IL-13 single-nucleotide polymorphisms (SNPs). However, there are only few studies regarding multiple sclerosis (MS) risk and IL-13 rs20541 (R130Q) polymorphism, and their results are conflicting. Therefore, the aim of our study was to investigate the frequency of the IL-13 gene rs20541 (R130Q) polymorphism in MS participants and its association with MS clinical subsets in the Polish population. We conducted a case‒control study including 94 relapsing remitting MS patients and 160 healthy volunteers. We genotyped the rs20541 polymorphism in the IL-13 gene and analysed the genotype frequency, age of MS onset and clinical condition (EDSS values) of the MS participants. Fisher’s exact test was used for statistical analysis, and the log-linear model was applied to test for associations. Allele A, as well as the AA and AG genotypes, was observed to be significantly more common in the MS subjects. The OR (odds ratio) for the A compared to the G allele was 1.71 (1.14–2.56), whereas OR 2.33 (0.86–6.26) and OR 1.92 (1.11–3.30) were obtained for the AA and AG genotypes, respectively. We did not identify any significant associations of the studied IL-13 SNP with the investigated clinical parameters of the MS participants. Our results suggest that the rs20541 polymorphism in the IL-13 gene may play an important role in MS predisposition but not in investigated clinical parameters in MS subjects of the Polish population.

IL-6, IL-10 and TNF-α gene polymorphisms in preeclampsia: a case-control study in a Mexican population.

We focused our study on examining the genotype and allele frequency of IL-6 (rs1800795), TNF-α (rs1800629) and IL-10 (rs1800872) single nucleotide polymorphisms (SNP) on preeclampsia (PE) diagnosed Mexican pregnant women. A case-control study was designed including 86 preeclampsia patients and 100 normotensives pregnancies from Women's Hospital of Culiacan, Mexico. Genotyping of IL-6, TNF-α and IL-10 was performed using TaqMan SNP Genotyping. Not significant association was found between development of PE and genotypic (p > 0.05) and allelic (p > 0.05) frequencies of IL-6, TNF-α and IL-10 SNPs. Genotype distributions of IL-6 (p = 0.599), TNF-α (p = 0.721) and IL-10 (p = 0.761) polymorphisms in the two groups were in agreement with Hardy-Weinberg equilibrium. According to the findings, the IL-6, TNF-α and IL-10 SNPs are not exponents of susceptibility to developing PE.

Rs1800890 Polymorphism of IL-10 and Susceptibility to Idiopathic Thrombocytopenic Purpura

AbstractImmune thrombocytopenic purpura (ITP) is an immune bleeding disorder that is reported in approximately 2 out of every 100,000 adults with a mean age of 50 years. Several factors such as various genetic backgrounds are associated with the pathogenesis of ITP. Interleukin (IL)-10 is a complicated cytokine that has a role in tumor progression, antitumor immunity, and immune system regulation. rs1800890 is an IL-10 single nucleotide polymorphism linked to lower levels of IL-10. A total of 67 patients with ITP and 70 healthy individuals (controls) were considered in this study. The IL-10 polymorphism was detected by the amplification refractory mutation system–polymerase chain reaction technique. According to our analysis, individual carriers of the AA genotype were less likely to develop ITP. The AT genotype was more common in patients with ITP in comparison to the control group. However, there was no significant association between rs1800890 genotypes (p = 0.775, odds ratio =1.517, 95%) in the acute and chronic groups. We observed that women had a higher mean frequency of this polymorphism (p = 0.0012). The rs1800890 AA genotype was associated with the highest platelet counts. However, the mean platelet volume and platelet distribution width values among alleles of the polymorphisms did not vary significantly. The IL-10 rs1800890 polymorphism may have a role in idiopathic thrombocytopenic purpura etiology. As a result, more research with a larger number of sample sizes is suggested.

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.

Cytokines Single Nucleotide Polymorphisms (SNPs) Association With Myasthenia Gravis (MG) In Algerian Patients: A Case-Control Study On A Small Group.

Myasthenia gravis (MG) is an autoimmune disease of multifactorial etiology in which genetic factors and cytokines seem to play an important role. The aim of this study was to investigate potential associations of cytokines single nucleotide polymorphisms (SNPs) and MG in Algerian patients. We performed a case-control study that included 27 patients and 74 healthy subjects. Cytokines SNPs genotyping was performed by the polymerase chain reaction sequence-specific primers (PCR-SSP) method. Our results showed that the TNF-α -308G/A (P < 0.005) and TGF-β1 +869T/T (P < 0.05) genotypes were more frequent among patients with MG compared with healthy individuals, whereas TNF-α -308G/G (P < 0.0001), TGF-β1 +869T/C (P < 0.05), and IFN-γ +874A/A (P < 0.05) were less frequent. Our results also showed that IL-10 and IL-6 SNPs did not show any significant difference in distribution between MG patients and healthy individuals. Our observations support the hypothesis that implicates genetic variants of certain cytokines in MG. However, ours results should be replicated with a larger sample size. In addition, the precise underlying processes remain to be clarified. TNF-α -308G/A and TGF-β1 +869T/C genotypes predispose to MG.IFN-γ +874A/A genotype protects against MG.IL-6 -174C/G SNP is not associated with MG.

Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitisB virus infection in Caucasians.

Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitisB virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population. A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitisB envelope antigen (HBeAg) negative chronic hepatitisB (n=255), with HBeAg positive chronic hepatitisB (n=99) and with HBeAg negative HBV infection (n=228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n=195) and in healthy controls (n=160). In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR=1.75, 95% CI 1.04-2.94, p=0.034), with an increased likelihood of HBeAg negative chronic infection (OR=1.93, 95% CI 1.05-3.54, p=0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07-3.39, p=0.029) in male patients. The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.

Cytokine Gene Polymorphisms in Patients with Chronic Inflammatory Demyelinating Polyneuropathy.

Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 (rs1800896, rs1800871, rs1800872 and rs3024505), IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients (p = 0.049), but the GA genotype prevailed among the patients (p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs (p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 (p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients (p = 0.049) and the CG heterozygote in the HCs (p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier (p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations.

Influence of IL-6 rs1800795 and IL-8 rs2227306 polymorphisms on COVID-19 outcome.

Severe coronavirus disease 2019 (COVID-19) is mainly precipitated by an uncontrolled inflammatory response and cytokine storm. Pro-inflammatory cytokines such as IL-6 and IL-8 levels were markedly increased in complicated cases. Genetic polymorphisms may have a role in this dysregulated expression during SARS-CoV-2 infection. Our aim was to assess the influence of IL-6 and IL-8 single nucleotide polymorphisms (SNPs) on COVID-19 outcomes. 240 subjects were involved in the study; 80 cases with severe COVID-19, 80 cases with mild COVID-19, and 80 healthy subjects. IL-6rs1800795(G/C) and IL-8 rs2227306(C/T) genotyping was performed using real-time polymerase chain reaction (PCR). Ages ranged between 20-67 years in all groups. There was a statistically significant association between the male gender and severe COVID-19. A significantly higher expression of IL-6rs1800795GG and IL-8rs2227306CC genotypes was observed among patients with severe COVID-19 than other groups. At the allele level, IL-6rs1800795G and IL-8rs2227306C alleles were more frequent among patients with severe COVID-19 when compared with other groups. Haplotypes' frequency clarified that the coexistence of IL-6 rs1800795G and IL-8rs2227306C alleles in the same person increased the risk of severe COVID-19 outcomes. Carriers of IL-6rs1800795C and IL-8 rs2227306T alleles are at lower risk of developing severe COVID-19. Multivariate logistic regression analysis showed that old age, male gender, IL-6 rs1800795CG+GG, and IL-8 rs2227306CT+CC genotypes could be independent risk factors for severe COVID-19 outcomes. IL-6 rs1800795G and IL-8 rs2227306C alleles are significantly associated with severe COVID-19 outcomes, especially if they coexist. They may be used as prognostic markers for COVID-19.

Polymorphism Analysis of Interleukin-18 and Interleukin-37 Genes in Hepatitis B Infections with Different Outcomes: A Preliminary Report from an Iranian Population.

Given the vital role of cytokines in influencing the outcomes of hepatitis B virus (HBV) infections, this study aimed to investigate the association between polymorphisms of interleukin (IL)-18 and IL-37 and the outcomes of HBV infection. In this study, we enrolled 300 subjects with chronic HBV infection, including those with cirrhosis/hepatocellular carcinoma (C/HCC), chronic active hepatitis B (CAH) infection, or asymptomatic carriers (AC), and 58 individuals whose infection was spontaneously cleared (SC). Genomic DNA was extracted, and IL-18/IL-37 genotyping was performed using PCR-RFLP and ARMS-PCR. The frequency of genotypes and alleles of IL-18 single nucleotide polymorphisms (SNPs) at positions rs1946519, rs1946518, and rs187238 and IL-37 at position rs4241122 were not statistically different among the four studied groups (P>0.05). Furthermore, the frequency of different haplotypes was similar among the studied groups (P>0.05). Polymorphisms of IL-18 SNPs at positions rs1946519, rs1946518, and rs187238 and variation of IL-37 at position rs4241122 do not appear to influence the outcome of HBV infection.

Plasma Cytokine Levels and Cytokine Genetic Polymorphisms in Patients with Metastatic Breast Cancer Receiving High-Dose Chemotherapy

Differences in the baseline levels of serum cytokines or in single-nucleotide polymorphisms (SNPs) in cytokine genes may be useful to predict outcomes for patients being treated for metastatic breast cancer. We have measured the plasma levels and characterized individual SNPs for IL-1RA, IL-1β, IL-2, IL-6 and TNFα in 130 patients with metastatic breast cancer treated with high-dose chemotherapy. Patients were treated with high-dose cyclophosphamide (Group 1, 74 patients) or high-dose paclitaxel-containing regimens (Group 2, 56 patients). A high plasma level of IL-1RA and a SNP in the IL-1RA gene indicated a better prognosis for patients in Group 1 (but not Group 2). However, the level of plasma IL-1RA did not correlate with the SNP genotype. A high plasma level of IL-6 or TNFα indicated a poorer outcome for patients in Group 1 although the SNP genotypes for the IL-6 and TNFα SNPs were not associated with differences in outcome. The plasma levels of IL-1β and IL-2 and the genotype of the IL-1β SNPs did not indicate differences in outcome. Although, individually, plasma levels of cytokine or “risk” SNP genotypes may not indicate outcome, in combination there was an increased trend to predict outcome for patients treated with high-dose cyclophosphamide but not high-dose paclitaxel. These results suggest that the immune cytokines may be useful as prognostic biomarkers in the treatment of patients with metastatic breast cancer treated with different types of chemotherapy.

Single nucleotide polymorphism of IL-18 gene and resistin gene in children infection with Entamoeba histolytica

Abstract Background: Human amebiasis is caused by Entamoeba histolytica, which is found in many tropical countries. E. histolytica infections are known to have a wide range of clinical consequences. Most infections are asymptomatic; some cause diarrhea and dysentery, and only a few cause extraintestinal consequences, including liver abscess. Single nucleotide polymorphisms (SNPs) are the most prevalent kind of sequence variation in genomes and are regarded as useful genetic markers for exposing the evolutionary history and common genetic variants that explain the heritable risk for common illnesses and effected in the progression of some infections. Objective: Investigation of gene polymorphism of the parameters (interleukin 18 [IL-18], resistin) most susceptible to parasitic infection. Materials and Methods: Stool samples were collected from patients who were attending the (Kerbala Teaching Hospital for children in the holy city of Kerbala), between February 2021 and January 2022. In total, 3748 samples of feces from children between the ages of 1 and 15 years from both gender were tested using both direct smear and acid-fast stain tests in addition to rapid test techniques. Five milliliters of blood were obtained from 25 patients infected with E. histolytica, as well as 5 mL of blood from 25 healthy youngsters (sample control). Results: The result showed the distribution of genotype of IL-18 SNPs in intestinal parasites patient in contrast to the control group; there is an increase in the level of IL-18 in some SNPs, resistin concentration was statistically significantly different between resistin gene polymorphisms. Conclusion: The IL-18 and resistin polymorphism can be considered one of the genetic factors responsible for the progression of E. histolytica infection.

Association of Single-Nucleotide Polymorphisms in Interleukin Genes with Microbial Keratitis in a South Indian Population

To examine the relationship between single-nucleotide polymorphisms (SNPs) in interleukin (IL) genes and keratitis and its clinical manifestations. SNPs in IL1B, IL6, CXCL8, IL10, and IL12B were analysed. Differences in frequencies of alleles, genotypes and haplotypes between cases and controls as well as associations between SNPs and clinical variables were calculated by χ2 tests with odds ratios. The minor homologous genotype in IL1B rs16944 (p = 0.036; odds ratio (OR) = 2.063, 95% confidence interval (CI): 1.048-4.061) and CXCL8 rs4073 (p = 0.041; OR = 0.463, 95% CI: 0.224-0.956) and the heterologous genotypes in IL6 rs1800795 (p = 0.046; OR = 0.563, 95% CI: 0.326-0.972) and IL12B rs2569254 (p = 0.0446; OR = 0.557, 95% CI: 0.314-0.989) or rs730691 (p = 0.0051; OR = 0.451, 95% CI: 0.260-0.784) were associated with keratitis. The minor genotype of rs16944 was associated with severe infection (p = 0.046). The heterologous genotype in rs2569254 was associated with hospital admission, photophobia, and mode of contact lens wear (p ≤ 0.041). The heterologous genotype in rs730691 was associated with blurred vision, discharge, anterior chamber reaction, and mode of wear (p ≤ 0.047). This study demonstrates that SNPs in IL1B and CXCL8 are associated with risk of developing keratitis. The study also found relationships between SNPs and clinical measures of keratitis. The potential for ethnic differences in frequency of SNPs and their association with keratitis should be followed up using different populations.

Interleukin-10 promoter variability is associated with the susceptibility, severity, and clinical outcomes of aplasitc anemia in Han-Chinese population.

Acquired aplastic anemia (AA), a heterogeneous bone marrow (BM) failure disease, is mainly mediated by the immune destruction of hematopoietic stem cells (HSCs). Given the predominant role of immunosuppressive therapy (IST) in AA, it is sensible to theorize that variants of cytokine genes might affect the outcome of IST. In this study, we analyzed three single nucleotide polymorphisms (SNPs) of interleukin (IL)-10 gene in promoter region to clarify their relationship with susceptibility, clinical efficacy and prognosis of AA. We observed that CT genotype of IL-10 rs1800896 was associated with a decreased risk of AA (adjusted OR=0.541 [95% CI 0.295-0.993], p=.047). Besides, the disease severity differed considerably by IL-10 gene promoter genotypes and alleles. Furthermore, IL-10 SNPs influenced efficacy of IST, with unfavorable response exhibited by rs1800871 and rs1800872 in dominant models (GG + AG vs. AA, adjusted OR=0.409 [95% CI 0.178-0.943, p=.036] for rs1800871 and GG + GT vs. TT, adjusted OR=0.396 [95% CI 0.173-0.909, p=.028] for rs1800872, respectively). The polymorphisms of IL-10 promoter region were informatively genetic risk factors which might be conducive to the insights into the mechanisms of AA and the design of individual regimens.

GENETIC VARIANTS AND SERUM PROFILES OF CYTOKINES IN COVID-19 SEVERITY.

Background: Patients with severe coronavirus disease 2019 (COVID-19) are at an increased risk of acute respiratory distress syndrome and mortality. This is due to the increased levels of pro-inflammatory cytokines that amplify downstream pathways that are controlled by immune regulators. Objective: This study aimed to investigate the association between cytokine genetic variants, cytokine serum levels/profiles, and disease severity in critically and noncritically ill COVID-19 patients. Methods: This cross-sectional study recruited 646 participants who tested positive for severe acute respiratory syndrome coronavirus 2 from six collection sites across the United Arab Emirates. Medical files were accessed to retrieve clinical data. Blood samples were collected from all participants. Patients were divided into two clinical groups, noncritical (n = 453) and critical (n = 193), according to World Health Organization classification guidelines for COVID-19 patients. Cytokine analyses were conducted on serum of a subset of the cohort, specifically on 426 participants (noncritical, 264; critical, 162). Candidate gene analyses of 33 cytokine-related genes (2,836 variants) were extracted from a genome-wide association study to identify genetic variants with pleiotropic effects on a specific cytokine and the severity of COVID-19 disease. Results: Age, body mass index (BMI), and pre-existing medical conditions were found to be significant risk factors that contribute to COVID-19 disease severity. After correcting for age, sex, and BMI, IP-10 ( P < 0.001), IFN ( P = 0.001), IL-6 ( P < 0.001), and CXCL-16 ( P < 0.001) serum levels were significantly higher among critical COVID-19 cases, when compared with noncritically ill patients. To investigate if the genetic variants involved in the serum cytokine levels are associated with COVID-19 severity, we studied several genes. Single nucleotide polymorphisms in IL6 (rs1554606; odd ratio (OR) G = 0.67 [0.66, 0.68]; P = 0.017), IFNG (rs2069718; OR G = 0.63 [0.62, 0.64]; P = 0.001), MIP (rs799187; OR A = 1.69 [1.66, 1.72]; P = 0.034), and CXCL16 (rs8071286; OR A = 1.42 [1.41, 1.44]; P = 0.018) were found to be associated with critically ill patients. Polymorphisms in the CXCL10 , CCL2 , IL1 , CCL7 , and TNF genes were not associated with the COVID-19 critical phenotype. The genotypes of IL-6 (gene, IL6 [7p15.3]) and CXCL-16 (gene, CXCL16 [17p13.2]) were significantly associated with the serum levels of the respective cytokine in critical cases of COVID-19. Conclusion: Data obtained from measuring cytokine levels and genetic variant analyses suggest that IL-6 and CXCL-16 could potentially be used as potential biomarkers for monitoring disease progression of COVID-19 patients. The findings in this study suggest that specific cytokine gene variants correlate with serum levels of the specific cytokine. These genetic variants could be of assistance in the early identification of high-risk patients on admission to the clinic to improve the management of COVID-19 patients and other infectious diseases.

Post-COVID Pain Is Not Associated with Inflammatory Polymorphisms in People Who Had Been Hospitalized by COVID-19.

Our aim was to assess the association between four inflammatory polymorphisms with the development of post-COVID pain and to associate these polymorphisms with the clinical pain phenotype in individuals who had been hospitalized by COVID-19. Three potential genotypes of IL-6 (rs1800796), IL-10 (rs1800896), TNF-α (rs1800629), and IFITM3 (rs12252) single nucleotide polymorphisms (SNPs) were obtained from no-stimulated saliva samples from 293 (49.5% female, mean age: 55.6 ± 12.9 years) previously hospitalized COVID-19 survivors by polymerase chain reactions. Pain phenotyping consisted of the evaluation of pain features, sensitization-associated symptoms, anxiety levels, depressive levels, sleep quality, catastrophizing, and kinesiophobia levels in patients with post-COVID pain. Analyses were conducted to associate clinical features with genotypes. One hundred and seventeen (39.9%) patients experienced post-COVID pain 17.8 ± 5.2 months after hospital discharge. No significant differences in the distribution of the genotype variants of any SNPs were identified between COVID-19 survivors with and without post-COVID pain (all, p > 0.47). Similarly, the clinical pain phenotype was not significantly different between patients with and without post-COVID pain since no differences in any variable were observed for any SNPs. In conclusion, four SNPs associated with inflammatory and immune responses did not appear to be associated with post-COVID pain in previously hospitalized COVID-19 survivors. Further, neither of the SNPs were involved in the phenotyping features of post-COVID pain.