IL6 Rs1800795 Research Articles

Predicting the risk of developing vibration disease and vegetative-sensory polyneuropathy under vibration exposure using analysis of candidate gene polymorphism

In this study, we investigated the association of IL-6 (rs1800795), TNF-α (rs361525), IL-1β (rs16944), MMP-1 (rs1799750) and SOD2 (rs4880) gene polymorphisms with the risk of developing vibration disease (VD) and autonomic sensory polyneuropathy (ASPN). We examined 45 patients with VB, 10 patients with ASPN and 76 people who were not exposed to vibration in their professional activities. Polymorphic gene variants were determined using a real-time polymerase chain reaction. The polymorphic variant rs16944 of the IL-1β gene was established to carry both the G allele (p = 0.027) and the homozygous G/G genotype (p = 0.015) with elevated frequency in the group of patients with VD relative to the control group. Allele A of the rs361525 polymorphic variant of the TNF-α gene was more common in patients with ASPN as compared to controls, (p = 0.047). Statistically significant differences in polymorphic variants rs1800795 of the IL-6 gene, rs1799750 of the MMP-1 gene and rs4880 of the SOD2 gene were not found in both groups of patients as compared to the control group. However, when comparing groups of patients with each other, we established that the G allele of the polymorphic variant rs1800795 of the IL-6 gene was more often recorded in patients with ASPN (p = 0.032). The results obtained by examining the patients with VD and ASPN made it possible to establish that the rs361525 polymorphic variant of the TNF-α gene is associated with an elevated risk of developing ASPN, while carriers of the homozygous genotype G/G of the rs16944 polymorphic variant of the IL-1β gene have a high prognostic risk of developing VD. Polymorphic variants of the IL-1β and TNF-α genes can be considered probable molecular genetic predictors of VD and ASPN.

Прогнозирование риска развития вибрационной болезни и вегетативно-сенсорной полинейропатии при вибрационном воздействии с исполь-зованием анализа полиморфизма кандидатных генов

In this study, we investigated the association of IL-6 (rs1800795), TNF-α (rs361525), IL-1β (rs16944), MMP-1 (rs1799750) and SOD2 (rs4880) gene polymorphisms with the risk of developing vibration disease (VD) and autonomic sensory polyneuropathy (ASPN). We examined 45 patients with VB, 10 patients with ASPN and 76 people who were not exposed to vibration in their professional activities. Polymorphic gene variants were determined using a real-time polymerase chain reaction. The polymorphic variant rs16944 of the IL-1β gene was established to carry both the G allele (p = 0.027) and the homozygous G/G genotype (p = 0.015) with elevated frequency in the group of patients with VD relative to the control group. Allele A of the rs361525 polymorphic variant of the TNF-α gene was more common in patients with ASPN as compared to controls, (p = 0.047). Statistically significant differences in polymorphic variants rs1800795 of the IL-6 gene, rs1799750 of the MMP-1 gene and rs4880 of the SOD2 gene were not found in both groups of patients as compared to the control group. However, when comparing groups of patients with each other, we established that the G allele of the polymorphic variant rs1800795 of the IL-6 gene was more often recorded in patients with ASPN (p = 0.032). The results obtained by examining the patients with VD and ASPN made it possible to establish that the rs361525 polymorphic variant of the TNF-α gene is associated with an elevated risk of developing ASPN, while carriers of the homozygous genotype G/G of the rs16944 polymorphic variant of the IL-1β gene have a high prognostic risk of developing VD. Polymorphic variants of the IL-1β and TNF-α genes can be considered probable molecular genetic predictors of VD and ASPN.

No Association of Polymorphisms in the Genes Encoding Interleukin-6 and Interleukin-6 Receptor Subunit Alpha with the Risk of Keloids in Polish Patients.

A keloid is a benign fibroproliferative hypertrophy of scar tissue that extends outside the original wound and invades adjacent healthy skin. Keloid formation is thought to be a complex process including overactivity of the interleukin-6 signaling pathway and genetic susceptibility. The aim of the study was to investigate possible associations between rs1800797, rs1800796, and rs1800795 polymorphisms in the promoter of the IL6 gene encoding interleukin-6 and the rs2228145 polymorphism in the IL6R gene encoding the interleukin-6 receptor subunit alpha with the predisposition to keloids in Polish patients. The genetic polymorphisms were identified either using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) or sequencing of samples of genomic DNA extracted from blood leukocytes of 86 adult patients with keloids and 100 newborns comprising a control group. No significant differences in the distributions of IL6 or IL6R alleles or genotypes were found between keloid patients and newborn controls. There were also no significant differences between both groups in the distribution of IL6 haplotypes. The IL6 rs1800797, rs1800796 and rs1800795 and IL6R rs2228145 polymorphisms were not found to predispose individuals in the study group to keloids. IL6 promoter haplotypes were not found to be associated with a higher risk of keloids in the studied group.

Effect of IL-2 polymorphism rs2069762 on single-unit cord blood transplant outcomes

BackgroundInterleukin-2 (IL-2) is one of the most important cytokines that regulate the activation and proliferation of T cells and natural killer cells. The production of IL-2 may be affected by polymorphisms in the promoter region of the IL-2 gene (rs2069762). In allogeneic hematopoietic cell transplantation (HCT) from adult donors, rs2069762 has been associated with the incidence of acute and chronic graft-versus-host disease (GVHD). However, the impacts of IL-2 polymorphism on cord blood transplantation (CBT) outcomes remain unclear. ObjectiveThe objective of this study was to assess the impact of IL-2 polymorphism rs2069762 on transplant outcomes, such as hematopoietic recovery, GVHD, overall survival, relapse, and non-relapse mortality (NRM) after CBT. Study DesignWe conducted a retrospective analysis of data from adult patients who underwent single-unit CBT at our institution from November 2005 to March 2023 for whom DNA samples from recipients and donors were available. IL-2 genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs2069762. ResultsA total of 143 recipient and donor pairs were included in this study. The proportion of recipient IL-2 polymorphism rs2069762 was 48 % (n = 69) for AA, 42 % (n = 60) for CA, and 10 % (n = 14) for CC. The proportion of donor IL-2 polymorphism rs2069762 was 43 % (n = 61) for AA, 48 % (n = 69) for CA, and 9 % (n = 13) for CC. In the multivariate analysis, the use of an rs2069762 CA + CC donor was associated with lower neutrophil recovery compared to an rs2069762 AA donor (hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.50–0.88; P = 0.004). Furthermore, recipients of rs2069762 CA + CC were associated with higher NRM compared to recipients of rs2069762 AA (HR, 2.32; 95 % CI, 1.01–5.34; P = 0.047). Serum IL-2 levels at 8 weeks were significantly higher in rs2069762 CA + CC recipients compared to those with rs2069762 AA recipients (P = 0.014). ConclusionOur data showed that donor IL-2 polymorphism affects neutrophil recovery and recipient IL-2 polymorphism affects NRM in adults undergoing single-unit CBT. The polymorphism of IL-2 rs2069762 in recipients and donors might be associated with the clinical outcomes of single-unit CBT.

Polymorphism of Genes Encoding Inflammatory Interleukins and the Risk of Anterior Cruciate Ligament Injury: A Systematic Review and Meta-Analysis.

Sport injuries, including the anterior crucial ligament rupture (ACLR) seem to be related to complex genetic backgrounds, including the genes responsible for inflammatory response. This review and meta-analysis investigated the contribution of the polymorphisms of genes encoding inflammatory cytokines and their receptors to the risk of ACLR. The scientific databases Science Direct, EBSCO host, Scopus, PubMed, and Google Scholar were screened (completed on 14 June 2023) according to the established inclusion/exclusion criteria (only fully accessible, original, human case-control studies written in English concerning the effect of interleukin genes' polymorphisms on the occurrence of ACL injury were included) and statistical meta-analysis using R version 4.0.3 was performed. The PRISMA methodology was used to review articles. The review protocol was registered under the number CRD42024514316 in the Prospero database. Eighty-nine studies were identified and narrowed down to three original case-control studies used for the meta-analysis. The studies analyzed Polish, South African, and Swedish cohorts, altogether 1282 participants. The candidate polymorphisms indicated in the studies involved IL6 rs1800795, IL6R rs2228145 and IL1B rs16944. The systematic review showed the relationships between IL6 rs1800795 polymorphism and ACLR in the Polish subpopulation, and IL6R rs2228145 and IL1B rs16944 in the South African subpopulations. The meta-analysis revealed that the IL6 rs1800795 CG genotype was over-represented (OR = 1.30, 95% CI 1.02-1.66), while the CC genotype was under-represented (OR = 0.75, 95% CI 0.54-1.03) in ACLR subjects, but no significant impact of IL6R rs2228145 was shown. Additionally, a tendency of the IL1B rs16944 CT genotype to be protective (OR 0.89, 95% CI 0.70-1.14), while the TT to be a risk genotype (OR 1.19, 95% CI 0.84-1.68) was observed. Thus, the relationship between the interleukin receptor IL6R rs2228145 and ACLR risk was not confirmed. However, the impact of genes coding pleiotropic IL6 rs1800795 on the incidences of ACLR was clear and the effect of pro-inflammatory IL1B rs16944 was possible.

Genetic variations in immune mediators and prostate cancer risk: A field synopsis with Bayesian calculations

ObjectiveOur study aimed to revaluate the significant data from meta-analyses on genetic variations in immune mediators and the risk of prostate cancer (PCa) by Bayesian approaches. MethodsWe performed a search on the literature before September 5th, 2023, for meta-analytic studies on polymorphisms in immune mediator genes and the risk of PCa. Two Bayesian approaches were used to assess the level of noteworthiness in the meta-analytic data: the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10−3 and 10−6. The quality evaluation of studies was performed with the Venice criteria. Gene-gene and protein–protein networks were designed for the genes and products enrolled in the results. ResultsAs results, 18 meta-analyses on 17 polymorphisms in several immune mediator genes were included (IL1B rs16944/rs1143627, IL4 rs2243250/rs2227284/rs2070874, IL6 1800795/rs1800796/rs1800797, IL8 rs4073, IL10 rs1800896/rs1800871/rs1800872, IL18 rs1946518, COX2 rs2745557, TNFA rs361525 and PTGS2 rs20417/689470). The Bayesian calculations showed the rs1143627 and the rs1946518 polymorphisms in IL1B and IL18 genes, respectively, were noteworthy. The Venice criteria showed that only four studies received the highest level of evidence. The gene-gene and protein–protein networks reinforced the findings on IL1B and IL18 genes. ConclusionIn conclusion, this current Bayesian revaluation showed that the rs1143627 and the rs1946518 polymorphisms in the IL1B and IL18 genes, respectively, were noteworthy biomarker candidates for PCa risk.

IL-10 and IL-1β Serum Levels, Genetic Variants, and Metabolic Syndrome: Insights into Older Adults' Clinical Characteristics.

Populational aging is marked by chronic noncommunicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarly, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

The interaction effect of dietary selenium intake and the IL10 rs1800871 polymorphism on the risk of colorectal cancer: a case-control study in Korea.

The importance of Se in human health has received much attention due to its antioxidant properties when it is consumed at an appropriate level. However, the existing evidence is limited to obtain an effective conclusion for colorectal cancer (CRC). Notably, an adequate intake of Se was reported for Koreans. Furthermore, cytokine secretion and immune function may be affected by dietary Se. Our study aimed to explore whether Se potentially reduces CRC risk and whether the IL10 rs1800871 polymorphism has an effect on this association. We designed a case-control study with 1420 cases and 2840 controls. A semi-quantitative FFQ was used to obtain information on Se intake. We determined IL10 rs1800871 through genetic analysis. Different models were developed to explore Se intake related to CRC risk by calculating OR and 95 % CI using unconditional logistic regression. A reduced risk of CRC was found as Se intake increased, with an OR (95 % CI) of 0·44 (0·35, 0·55) (Pfor trend < 0·001). However, this association seems to be allele-specific and only present among risk variant allele carriers (GA/GG) with a significant interaction between dietary Se and IL10 rs1800871 (Pfor interaction = 0·043). We emphasised that a reduction in CRC risk is associated with appropriate Se intake. However, the IL10 rs1800871 polymorphism has an impact on this reduction, with a greater effect on variant allele carriers. These findings suggest the importance of considering an individual's genetic characteristics when developing nutritional strategies for CRC prevention.

The role of longevity-related genetic variant interactions as predictors of survival after 85 years of age

Genome-wide association studies and candidate gene studies have identified several genetic variants that might play a role in achieving longevity. This study investigates interactions between pairs of those single nucleotide polymorphisms (SNPs) and their effect on survival above the age of 85 in a sample of 327 Croatian individuals. Although none of the SNPs individually showed a significant effect on survival in this sample, 14 of the 359 interactions tested (between SNPs not in LD) reached the level of nominal significance (p<0.05), showing a potential effect on late-life survival. Notably, SH2B3 rs3184504 interacted with different SNPs near TERC, TP53 rs1042522 with different SNPs located near the CDKN2B gene, and CDKN2B rs1333049 with different SNPs in FOXO3, as well as with LINC02227 rs2149954. The other interaction pairs with a possible effect on survival were FOXO3 rs2802292 and ERCC2 rs50871, IL6 rs1800795 and GHRHR rs2267723, LINC02227 rs2149954 and PARK7 rs225119, as well as PARK7 rs225119 and PTPN1 rs6067484. These interactions remained significant when tested together with a set of health-related variables that also had a significant effect on survival above 85 years. In conclusion, our results confirm the central role of genetic regulation of insulin signalling and cell cycle control in longevity.

Immune gene polymorphisms associated with poor response to platelet transfusion and recombinant factor VII administration in Glanzmann thrombasthenia.

Poor response to platelet and recombinant factor VII administration is a major problem in patients with Glanzmann Thrombasthenia (GT). The risk factors associated with poor response to treatment in these patients are unknown. Some genetic variations of cytokines may contribute to therapy resistance. We evaluated, for the first time, whether genetic polymorphisms on cytokine genes are related to poor treatment response in GT patients. We enrolled 30 patients with GT (15 resistant and 15 non-resistant) and 100 healthy controls. Gene polymorphisms of IL-10 and TNF-α were analysed using TaqMan Realtime PCR, and IL-1, IL-1R1 and IL-1RN were investigated with the RFLP method. In-silico analyses were performed to predict the potential impact of these polymorphisms. In the resistant group, all patients had a variant of the IL-10 gene at the -1082 position (rs1800896), with a GG genotype that was significantly more frequent than the non-resistant group. Analysis between healthy controls and GT patients revealed a probable correlation between rs3783550, rs3783553, rs3917356 and rs2234463 and GT. The In-silico study indicated that TNF-α rs1800629 and IL-10 rs1800896 polymorphisms result in different allelic expressions which may contribute to poor response to therapy. These findings suggest that polymorphisms in the IL-10 and IL-1 receptor antagonist genes may play a role in poor therapy response in GT patients. In addition, some polymorphisms in IL-1α, IL1-β, IL-1R1 and IL-R antagonists might be involved in the GT progression.

IL-18 and CD14 variants in chronic HBV predisposition: a case-control study with in silico analyses focused on transcription and splicing

Hepatitis B virus (HBV), a vaccine-avoidable infection, is a health concern worldwide, leading to liver disorders such as acute self-constraint and chronic hepatitis, liver failure, hepatic cirrhosis, and even hepatocellular carcinoma if untreated. ‘Immunogeneticprofiling’, genetic variations of the pro- and anti-inflammatory cytokines responsible for regulating the immune responses, cause person-to-person differences and impact the clinical manifestation of the disease. The current experimental–bioinformatics research was conducted to examine whether promoteric IL-18–rs187238 C > G and –rs1946518 T > G and intronic CD14–rs2569190 A > G variations are associated with chronic HBV. A total of 400 individuals (200 in each case and control group) participated in the study and were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The data was also assessed bioinformatics-wise for conservation, genomic transcription and splicing, and protein interactions. Findings proposed that unlike the IL-18–rs1946518 T > G and CD14–rs2569190 A > G, the IL-18–rs187238 C > G is a protector against chronic HBV (odds ratio [OR] = 0.62, 95% confidence intervals [CI]: 0.46–0.83, and p = 0.002). The TG/CC/AA, TG/CC/AG, TT/CC/AG, and GG/CC/AA combined genotypes significantly increased chronic HBV risk (p < 0.05), while the IL-18 G/T and G/G haplotypes lessened it (p < 0.05). Moreover, IL-18–rs1946518 T > G is in the protected genomic regions across mammalian species. In contrast to the IL-18–rs1946518 T > G, IL-18–rs187238 C > G is likely to create novel binding sites for transcription factors, and the CD14–rs2569190 A > G presumably changed the ribonucleic acid splicing pattern. More research on larger populations and other ethnicities is required to authenticate these results.

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.

Inflammatory Polymorphisms (IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252) Are Not Associated with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors.

The aim of this study was to identify the association between four selected inflammatory polymorphisms with the development of long-term post-COVID symptoms in subjects who had been hospitalized due to SARS-CoV-2 infection during the first wave of the pandemic. These polymorphisms were selected as they are associated with severe COVID-19 disease and cytokine storm, so they could be important to prognoses post-COVID. A total of 408 (48.5% female, age: 58.5 ± 14.0 years) previously hospitalized COVID-19 survivors participated. The three potential genotypes of the following four single-nucleotide polymorphisms, IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252, were obtained from non-stimulated saliva samples of the participants. The participants were asked to self-report the presence of any post-COVID symptoms (defined as symptoms that had started no later than one month after SARS-CoV-2 acute infection) and whether the symptoms persisted at the time of the study. At the time of the study (mean: 15.6, SD: 5.6 months after discharge), 89.4% of patients reported at least one post-COVID symptom (mean number of symptoms: 3.0; SD: 1.7). Fatigue (69.3%), pain (40.9%), and memory loss (27.2%) were the most prevalent post-COVID symptoms in the total sample. Overall, no differences in the post-COVID symptoms depending on the IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252 genotypes were seen. The four SNPs assessed, albeit having been previously associated with inflammation and COVID-19 severity, did not cause a predisposition to the development of post-COVID symptoms in the previously hospitalized COVID-19 survivors.

Association of IL-4 (− 590 C/T) and IL-6 (− 174 G/C) gene polymorphism in South Indian CKD patients

AimThe present study was undertaken to examine the role of IL-4 (− 590 C/T) (rs2243250) and IL-6 (− 174G/C) (rs1800795) polymorphism and the serum levels of IL-4 and IL-6 in chronic kidney disease (CKD).MethodsThe IL-4 (− 590C/T) and IL-6 (− 174 G/C) polymorphisms were genotyped in 132 CKD patients and 161 controls using PCR–RFLP. Serum IL-4 and IL-6 quantifications were performed by ELISA.ResultsSignificant susceptible associations of CT genotype (OR = 4.56; p < 1.84 × 10–9) and T allele (OR = 1.56; p < 0.010) of IL-4 (− 590C/T) and CC genotype (OR = 2.63; p < 0.032) of IL-6 (− 174G/C) were observed for CKD. The CC genotype (OR = 0.27; p < 9.314 × 10–7) and C allele (OR = 0.63; p < 0.010) of IL-4 (− 590 C/T) revealed strong protective associations. Five-fold increased levels were observed for both IL-6 (p < 0.0001) and IL-4 (p < 0.0043) cytokines in CKD patients than the controls. The IL-4 serum levels (pg/ml) increased significantly in patients with CT and TT genotypes of IL-4 (− 590 C/T) than the controls (6.18 ± 1.80 vs. 3.33 ± 0.48 and 6.14 ± 1.96 vs. 3.21 ± 0.56 respectively). For IL-6 (− 174 G/C) polymorphism, the patients with CC genotype (6.50 ± 1.30 vs. 3.49 ± 1.39) revealed with higher IL-6 serum levels followed by GC genotype (5.00 ± 1.91 vs. 4.01 ± 1.74).ConclusionThe genotypes of IL-4 (590 C/T) and IL-6 (174 G/C) polymorphisms contribute differential susceptibility in south Indian CKD patients. A fivefold increased serum levels of IL-4 (anti-inflammatory) and IL-6 (pro- and anti-inflammatory) cytokines were documented in CKD patients. There observed an opposite trend in disease association for these two cytokines and associated SNPs with CKD in south India.

Analysis of Mutational Status of IGHV, and Cytokine Polymorphisms as Prognostic Factors in Chronic Lymphocytic Leukemia: The Romanian Experience.

The aim of the current study was to assess the associations between genetic risk factors (such as the mutational status of the IGHV gene and polymorphisms of the IL-10 and TNF-α genes) and CLL risk, prognosis, and overall survival. Another goal of this study was to evaluate the multivariate effect of the combination of multiple genetic risk factors (mutational status of the IGHV gene, somatic mutations, DNA CNVs, and cytokine SNPs) on the clinical characteristics and survival of patients. A total of 125 CLL patients and 239 healthy controls were included for comparative SNP analysis. IL-10 (rs1800896 and rs1800872) and TNF-α (rs361525 and rs1800750) SNPs and haplotypes were not associated with CLL risk. The absence of hypermutation in the IGHV gene was shown to be of important prognostic value, being associated with short OS. Further individual risk factors for short OS were an age above 65 years at diagnosis and the presence of somatic mutations and/or CNVs. In our multivariable analysis, the presence of somatic mutations and the IL-10 rs1800872 variant allele, and the association of CNVs with the IL-10 rs1800896 variant allele, were identified as risk factors for short OS. Moreover, the OS in unmutated IGHV patients was additionally affected (decreased) by the presence of CNVs and/or somatic mutations. Similarly, IL-10 rs1800896 modulated the OS in unmutated IGHV patients with CNVs.

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.

Molecular Determination of Tumor Necrosis Factor-alpha, Interleukin-8, Interleukin-10, and C-X-C Chemokine Receptor-2 Genetic Variations and their Association with Disease Susceptibility and Mortality in COVID-19 Patients.

Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.

Role of the IL8 rs4073 polymorphism in central nervous system toxicity in patients receiving multidrug-resistant tuberculosis treatment.

To determine the role of the IL8 rs4073 polymorphism in predicting the risk of central nervous system (CNS) toxicity in patients receiving standard pharmacological treatment for multidrug-resistant tuberculosis (MDR-TB). A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed. The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype. The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.

Correlation between rs1800871, rs1800872 and rs1800896 Polymorphisms at IL-10 Gene and Lung Cancer Risk.

The tumorigenesis of lung cancer is complicated, and genetic factor may have the role in the malignant transformation of lung cells. IL-10 gene polymorphisms have been evaluated for their potential roles in lung cancer. However, those studies results are controversial. To clarify the effects of IL-10 rs1800871, rs1800872 and rs1800896 polymorphisms on the risk of lung cancer, a meta-analysis was performed with eligible individual studies. Eligible publications were gathered by retrieving PubMed, Web of Science, Embase, Wan Fang, and CNKI up to September 01, 2023. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association. A total of 23 studies, including 5950 patients with lung cancer and 8046 healthy controls, were identified in this meta-analysis. Overall, there was no a significant association between the rs1800871, rs1800872 and rs1800896 polymorphisms at IL-10 gene and susceptibility to lung cancer globally when all studies in the pooled into this meta-analysis. Stratified analysis by ethnicity showed that rs1800872 polymorphism was associated with lung cancer among Asians and Caucasians. However, no significant association was identified between the rs1800871 and rs1800896 and risk of lung cancer. Pooled data showed that IL-10 rs1800871, rs1800872 and rs1800896 polymorphisms were not associated with lung cancer globally. Future well-designed large case-control studies with different ethnicities are recommended.

Characterisation ofIGF-1 (rs7136446) and IL-6 (rs1800795) polymorphisms among breast cancer patients in western Algeria.

Breast cancer (BC) is themost frequently diagnosed cancer among women worldwide, including Algeria. Certain single nucleotide polymorphisms (SNPs) have been linked to higher risk ofBC. Several studies have been performed on theinsulin- like growth factor 1 (IGF-1) T > C (rs7136446) and theinterleukin 6 (IL-6) 174 G > C (rs1800795) SNPs to explore their role in BC. Theaim ofthis study is to investigate theassociation between the2 SNPs, IL-6 (rs1800795) and IGF-1 (rs7136446) with BC in thepopulation ofwestern Algeria. This study was carried out for thefirst time among theAlgerian population. This case-control study included 109 BC patients and 112 healthy controls. Genomic DNA was extracted from peripheral blood samples. DNA concentration was determined using theQubit 2.0 fluorometer. Thegenotyping ofselected SNPs was performed by real-time polymerase chain reaction followed by statistical analysis to assess genotypic frequencies and genetic association with BC. Theresults showed that IGF-1 rs7136446 was positively associated with BC (p = 0.00001) and that thedistribution ofgenotype frequencies ofrs7136446 showed astatistically difference between human epidermal growth factor receptor 2 (HER-2) positive and HER-2 negative BC (p = 0.04), but this association did not last after thecorrection ofBonferroni. No association was found in genotype distribution oftheIL-6 (rs1800795) among controls and BC patients or with clinicopathological parameters including HER-2 status in BC (p > 0.05). In summary, our findings indicate that IGF-1 rs7136446 is associated with BC in our population ofwestern Algeria.