Cytokine Polymorphisms Research Articles

Associations of Tumor Necrosis Factor–α G-308A (rs1800629) Gene Polymorphisms with Major Depressive Disorder

Pro-inflammatory cytokine polymorphisms like Tumor Necrosis Factor- (TNF), has been found associated to severe depressive disorder (MDD). The Pro-inflammatory cytokines tumor necrosis factor (TNF-α) G-308A (rs1800629) have been discovered to have an important role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. The present study aims to study TNF-α gene polymorphisms in Major depressive disorder using allele specific PCR. The results show that family history are non- significant different between patients and control group (0.6346) and also there was non- significant different in BMI (0.3417), The genotyping data show tow alleles and three genotyping (AG, GG, AA) the statically analysis show non-significant differences between patients and controls groups (0.095, 0.800) for GG, AA and GA respectively with more frequent of GA in patients than control group, the G allele was less frequent in patient than control while A allele was more frequent in patients than control group in significant differences (0.0001). It can be concluded that TNF genotyping didn’t impact in the Major depressive disorder but the allele distribution may have potential role in MDD patients.

Genetic polymorphisms of IL-27 and risk of systemic lupus erythematosus disease in the Egyptian population.

Cytokine polymorphisms have been associated with systemic lupus erythematosus (SLE) pathogenicity. Interleukin 27 (IL-27) is an important one of pro-/anti-inflammatory cytokine. It has been reported in various Th1/Th17-mediated inflammatory disorders, and even in Th2-complexed diseases, such as SLE. In our preliminary study, the aim was to investigate the potential roles of single nucleotide polymorphism (SNP) -964A/G (rs153109) and + 2905T/G (rs17855750) in an IL-27p28 gene on susceptibility to SLE. The 112 Egyptian SLE patients against 101 healthy persons were enrolled in this work. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) is used for genotyping IL-27 SNPs. No significant variations were found between patients and control in the genotype and allele frequencies of IL-27p28 (-964A/G). SLE patients have a significant increase in the frequency of IL-27p28 (+ 2905T/G) TG genotype (P < 0.01) and G allele (P < 0.01) compared to controls. Complete disappearance of GG genotype was demonstrated in both groups. G allele might have considered a disease risk factor with odd ration (OR) = 9.184. From four possible haplotypes, the frequency of AT haplotype elevated in both examined groups. This was the first study on the Egyptian population for studying the relation between IL-27 SNPs and SLE. Our preliminary study indicated that both TG genotype and G allele of IL-27p28 (+ 2905T/G) could consider risk factors for SLE. Key Points • This article provides an information about the relation between systemic lupus erythematosus and interleukin-27 cytokine by detection single nucleotide polymorphism.

Polymorphisms of Pro-Inflammatory IL-6 and IL-1β Cytokines in Ascending Aortic Aneurysms as Genetic Modifiers and Predictive and Prognostic Biomarkers.

Background: Previous studies have demonstrated that polymorphisms involved in immune genes can affect the risk, pathogenesis, and outcome of thoracic ascending aortic aneurysms (TAAA). Here, we explored the potential associations of five functional promoter polymorphisms in interleukin-6 (IL-6), IL-1B, IL-1A, IL-18, and Tumor necrosis factor (TNF)A genes with TAAA. Methods: 144 TAAA patients and 150 age/gender matched controls were typed using KASPar assays. Effects on telomere length and levels of TAAA related histopathological and serological markers were analyzed. Results: Significant associations with TAAA risk were obtained for IL-6 rs1800795G>C and IL-1B rs16944C>T SNPs. In addition, the combined rs1800795C/rs16944T genotype showed a synergic effect on TAAA pathogenesis and outcome. The combined rs1800795C/rs16944T genotype was significantly associated with: (a) higher serum levels of both cytokines and MMP-9 and -2; (b) a significant CD3+CD4+CD8+ CD68+CD20+ cell infiltration in aorta aneurysm tissues; (c) a significant shorter telomere length and alterations in telomerase activity. Finally, it significantly correlated with TAAA aorta tissue alterations, including elastic fragmentation, medial cell apoptosis, cystic medial changes, and MMP-9 levels. Conclusions: the combined rs1800795C/rs16944T genotype appears to modulate TAAA risk, pathogenesis, and outcome, and consequently can represent a potential predictive and prognostic TAAA biomarker for individual management, implementation of innovative treatments, and selection of the more proper surgical timing and approaches.

Influence of pro-inflammatory cytokines polymorphisms on the interrelationship between Graves’ disease and diabetes

Influence of pro-inflammatory cytokines polymorphisms on the interrelationship between Graves’ disease and diabetes

Association between idiopathic recurrent pregnancy loss and genetic polymorphisms in cytokine and matrix metalloproteinase genes.

Recurrent reproductive loss (RPL) is a global health issue affecting a significant number of women. Approximately half of miscarriages have an unexplained etiology. Familial aggregation and twins studies prove that some cases of the RPL could have a genetic background. Recent evidences suggest that cytokines (e.g. IL-6, TNF alpha or TGF beta) and matrix metalloproteinases (MMP) are important for maintenance of pregnancy. Single gene polymorphisms (SNP), affecting these proteins production or their function may predispose to the loss of the pregnancy. The aim of this study was to evaluate the association between the following polymorphisms of IL6 (rs1800795), TNF (rs1800629), TGFB1 (rs1800471), MMP1 (rs1799750), MMP2 (rs2285053 and rs243865), MMP3 (rs35068180), MMP9 (rs3918242) and the recurrent pregnancy loss in polish population. Study subjects comprised of 67 patients with a history of recurrent pregnancy loss (≥ 2 miscarriages in history) and 75 controls. The distribution of genotypes for selected polymorphisms were determined by RFLP-PCR. Maternal genotypes GG TNF, or 5A/5A MMP3 may be associated with the recurrent pregnancy loss. No association between the IL6, TGFB1, MMP1, MMP2, or MMP9 studied polymorphisms and the predisposition to miscarriage was found. This study demonstrated a possible association between rs1800629 TNF, rs35068180 MMP3 polymorphisms and recurrent pregnancy loss.

Associations of Serum Cytokine Levels and Interleukin-6-572C/G Polymorphism with Myelin Damage in Chinese Children with Autism Spectrum Disorder

Increasing evidence suggests that immunological disturbances and abnormalities in axonal myelination are involved in the pathophysiology of autism spectrum disorder (ASD). The present study aimed to determine the role of cytokines in myelin damage in Chinese children with ASD and the role of cytokine dysregulation, myelin damage, and cytokine polymorphisms in ASD in Chinese children. The present case-control study included 98 ASD subjects and 252 typically developing (TD) controls; the levels of serum cytokines and myelin basic protein (MBP) were determined using enzyme-linked immunosorbent assay. Cytokine polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Autistic clinical manifestations were assessed by the Childhood Autism Rating Scale (CARS). The results showed that serum levels of interleukin (IL)-1β, IL-2R, IL-6, IL-8, and MBP were higher in children with ASD compared with those in TD children. In individuals with ASD, serum MBP level was significantly positively associated with the CARS total score, and serum levels of IL-1β, IL-2R, IL-6, and MBP demonstrated positive correlations. The data identified IL-6*MBP as a factor that influenced the risk of ASD, and IL-2R*MBP was identified as a factor that influenced symptom severity, which influenced auxiliary diagnosis of ASD. The presence of the interleukin-6-572CC genotype was associated with significantly higher serum levels of IL-6 and MBP but did not influence the risk and symptom severity of ASD. Therefore, the results suggested inflammatory responses and myelin damage in Chinese children with ASD. Cytokine dysregulation influenced myelin damage in ASD; moreover, the interactions of the cytokines and myelin damage influenced the risk and symptom severity of ASD. The IL-6-572C/G genotypes may be associated with myelin damage in ASD by influencing the circulating level of IL-6.

Study of TNF-α, IFN-γ, TGF-β, IL-6, and IL-10 Gene Polymorphism in Individuals from the Leprosy-Endemic Area in the Brazilian Amazon.

This study aimed at verifying the relationship between the polymorphisms of the cytokines tumor necrosis factor-alpha (TNF-α) -308 G → A (rs1800629); interferon gamma (IFN-γ) +874 T → A (rs2430561); transforming growth factor-beta (TGF-β) códon 10 (rs1982073) and códon 25 (rs1800471); interleukin (IL)-6 - 174 G → C (rs180079) and IL-10 - 1082 A→T (rs1800896); -819 C → T (rs1800871); -592 A→C (rs1800872); and leprosy. Blood samples were analyzed from 106 individuals, of whom 24 were paucibacillary (PB), 28 were multibacillary (MB), and 54 were patient contacts. Analysis of cytokine polymorphisms was typified by the polymerase chain reaction technique. For TGF-β +869 T → C and +915 G→C, a tendency to associate the presence of the C allele at codon 10 with leprosy was demonstrated, with the T allele being most frequently found in the CCOSI (P = 0.056). For the polymorphisms IL-10 - 1082 A→T, -819 C→T, and -592 A→C, we found an association of the GCC/GCC genotype with the susceptibility to the disease and the A allele at position 1082 with the leprosy protection. Greater predominance was found of ACC/ATA (31.3%) and GCC/ATA (37.5%) (P = 0.03) and the A allele at position -1082 (76.85%) (P = 0.043) in the CCOSI groups, whereas the GCC/GCC was found in the MB group (22.2%) (P = 0.05). For the other cytokines's single-nucleotide polymorphisms, there were no associations with susceptibility to leprosy. These results are limited by sample size, may not be conclusive, and will need further confirmation in a larger cohort.

The TNF-A–857*T Polymorphism is Associated with Gastric Adenocarcinoma Risk in a Costa Rican Population

BackgroundCosta Rica is ranked as one of the countries with highest incidence of gastric cancer worldwide. Previous studies in Costa Rican populations have revealed associations between gastric cancer risk and several cytokine polymorphisms that seem to play a role in the regulation of the expression of these proteins. In this study, we assessed associations of the polymorphisms IL-6-174 G/C, IFNGR1-56 C/T, IL-8-251 T/A and TNF-A (-857 C/T, -308 A/G) with gastric pathologies in a high-risk population of Latin America. MethodsDNA samples of 47 patients with gastric adenocarcinoma, 53 with chronic gastritis, 56 with duodenal ulcer and 94 healthy controls, were genotyped for the five mentioned SNPs. All participants were ≥50-years-old. Genotyping was performed by PCR-RFLP and 5’-nuclease PCR assay. H. pylori infection, CagA status, pepsinogen (PG) I and II blood levels were determined by ELISA. Logistic regression analysis was used to determine possible associations of the polymorphisms with cancer, gastritis and duodenal ulcer, and linear regression analysis to determine associations with blood PG levels. ResultsA total of 86.6% of the population was positive for H. pylori; of them, 51.6% was CagA+. Patients with the TNF-A-857*T allele had an increased risk for gastritis (OR: 3.67, p = 0.015) and gastric adenocarcinoma (OR:6.15, p = 0.001). Associations between other polymorphisms and gastric diseases, or PG levels, were not found. ConclusionsOur results indicate that the TNF-A-857*T SNP is among the risk factors associated with the risk of gastric cancer in Costa Rica.

Predictive immunogenetic markers in COVID-19

Immunorelevant genes are among the most probable modulators of coronavirus disease 2019 (COVID-19) progression and prognosis. However, in the few months of the pandemic, data generated on host genetics has been scarce. The present study retrieved data sets of HLA-B alleles, KIR genes and functional single nucleotide polymorphisms (SNPs) in cytokines related to COVID-19 cytokine storm from two publicly available databases: Allele Frequency Net Database and Ensembl, and correlated these frequency data with Case Fatality Rate (CFR) and Daily Death Rates (DDR) across countries. Correlations of eight HLA-B alleles and polymorphisms in three cytokine genes (IL6, IL10, and IL12B) were observed and were mainly associated with DDR. Additionally, HLA-B correlations suggest that differences in allele affinities to SARS-CoV-2 peptides are also associated with DDR. These results may provide rationale for future host genetic marker surveys on COVID-19.

Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene\u2013gene and gene\u2013lifestyle interaction

Molecular and genetic immune-related pathways connected to breast cancer and lifestyles in postmenopausal women are not fully characterized. In this study, we explored the role of pro-inflammatory cytokines such as C-reactive protein (CRP) and interleukin-6 (IL-6) in those pathways at the genome-wide level. With single-nucleotide polymorphisms (SNPs) in the biomarkers and lifestyles together, we further constructed risk profiles to improve predictability for breast cancer. Our earlier genome-wide association gene-environment interaction study used large cohort data from the Women’s Health Initiative Database for Genotypes and Phenotypes Study and identified 88 SNPs associated with CRP and IL-6. For this study, we added an additional 68 SNPs from previous GWA studies, and together with 48 selected lifestyles, evaluated for the association with breast cancer risk via a 2-stage multimodal random survival forest and generalized multifactor dimensionality reduction methods. Overall and in obesity strata (by body mass index, waist, waist-to-hip ratio, exercise, and dietary fat intake), we identified the most predictive genetic and lifestyle variables. Two SNPs (SALL1 rs10521222 and HLA-DQA1 rs9271608) and lifestyles, including alcohol intake, lifetime cumulative exposure to estrogen, and overall and visceral obesity, are the most common and strongest predictive markers for breast cancer across the analyses. The risk profile that combined those variables presented their synergistic effect on the increased breast cancer risk in a gene–lifestyle dose-dependent manner. Our study may contribute to improved predictability for breast cancer and suggest potential interventions for the women with the risk genotypes and lifestyles to reduce their breast cancer risk.

Cytokine Levels and Polymorphisms in Childhood Asthma Among the Iranian Population

Context: Chronic airway inflammation in asthma is affected by a complex network of interacting cytokines. The exact role of each cytokine in childhood asthma development has remained poorly understood. In this study, we aimed to review articles investigating cytokine levels and polymorphisms in childhood asthma among the Iranian population to assess susceptible cytokines related to childhood asthma. Evidence Acquisition: We performed a literature search in PubMed, Scopus, Science direct, and Embase databases to find articles that have evaluated the cytokine levels and gene polymorphisms in childhood asthma among the Iranian population until March 2, 2020. The terms used to search included “cytokine”, “interleukin”, “polymorphism”, “Asthma”, and “Iran” in the international databases. Only case-control studies with a healthy control group that investigated cytokine levels and polymorphism in childhood asthma among the Iranian population have been included. Results: Considering these criteria, we extracted 7 articles from international databases and included them in the current review. We investigated 4 cytokine levels and 4 cytokine polymorphism patterns in asthmatic and non-asthmatic subjects in Iran. Interleukin (IL)-23, IL-17, and IL-33 levels were statistically higher in asthmatic children, and also IL-33, IL-17 levels were associated with asthma severity. There were no significant differences between healthy and asthmatic subjects regarding IL-35 levels. Polymorphisms in cytokine IL-4, IL-10, tumor necrosis factor (TNF)-α, and IL-2 were susceptible to childhood asthma in the Iranian population. Conclusions: Increased IL-33 and IL-17 levels were related to disease severity in childhood asthma. Four cytokine polymorphisms (IL-4, IL-10, IL-2, and TNF-α) were associated with the risk of pediatric asthma in the Iranian population.

Genetic Polymorphism of Tumor Necrosis Factor-Alpha, Interferon-Gamma and Interleukin-10 and Association With Risk of Mycobacterium Tuberculosis Infection.

Background. Mycobacterium tuberculosis has become the leading cause of morbidity and death in humans worldwide. Thus, genetic variability of the host plays a major role in human susceptibility to the pathogen, among others. Therefore, the objective of this finding was to assess the association of genetic polymorphisms of cytokines with tuberculosis infection.Method.A cross-sectional study was conducted between January and May 2018. Five ml of whole blood was collected and extracted the genomic DNA through simple salting out method. The patterns of genetic polymorphism were determined by amplification refractory method PCR using specific primers. Finally, the PCR run on electrophoresis of agarose gel and the band was visualized under UV light. A logistical regression model has been adapted to assess the association of genetic polymorphisms with tubercular infection. In order to determine the association between the explanatory and outcome variable, the odds ratio with 95% CI was calculated. P < 0.05 is a statistically significant value.Result.In present study, the frequency of TNF-α -308 G allele and GG genotype OR (95% CI)= 0.20 (0.11-0.37), and OR (95% CI)= 0.29 (0.18-0.46)), respectively) and IFN-γ +874 A allele and AA genotype OR (95% CI)= 3.80 (2.11-6.86) and (OR (95% CI)= 1.61(1.13-2.28), respectively) were significantly associated with tuberculosis incidence. In contrast, there is no significant correlation between IL-10 -1082 A and AA of allele and genotype, respectively in tuberculosis patients (p > 0.05) was evident.Conclusion.From our finding, the genetic variability of TNF-α -308 A and IFN-γ +874 alleles are the potent host genetic risk factors associated with tuberculosis infection.

Investigating the Association between IL-27 and Susceptibility to Preeclampsia among Iranian Women.

Preeclampsia (PE) is one of the most serious disorders of human pregnancy with a high rate of mortality for the fetus and mother. Several etiological factors are involved in the onset of this disease. Upregulation of IL-27 has been reported in placental tissue recovered from preeclamptic women, but the role of IL-27 has not yet been investigated in PE. The aim of the study was to investigate the association of IL-27 rs153109 and rs17855750 gene polymorphisms with PE; also, protein levels and susceptibility and severity of PE in Iranian women were evaluated. This case-control study was performed on 199 PE patients and 228 healthy women as the control group. IL-27 rs153109 and rs17855750 SNPs were genotyped using a PCR-RFLP method. Moreover, the levels of IL-27 were determined in 40 PE and 45 healthy women using ELISA method. Statistical analysis indicated that there were no differences in genotype, allele and genotype combination frequencies in the SNPs between cases and controls. The plasma level of IL-27 was elevated in the mild form of the disease compared with controls (p-value: 0.006). The effect of IL-27 in preeclampsia is not due to the studied cytokine polymorphisms, but the level of IL-27 might be associated with the severity of preeclampsia in Iranian women.

The role of interleukin 1β and interleukin 1 receptor antagonist polymorphism genes, Helicobacter pylori infection and the state of the gastric mucosa in the development and progression of gastroesophageal reflux disease

The mechanisms of the gastroesophageal reflux disease (GERD) development and its complications are analyzed on the tissue and cell levels. That’s why studying polymorphism of interleukin (IL) genes is important. Genotypes IL1β-511Т/Т, IL1β31С/С and IL1RN2/2 (receptor antagonist IL1) associate with high risk of complicated course of GERD disease. Researching genes polymorphism of the pro-inflammatory cytokines of the patients having gastroesophageal reflux disease and changes in gastric mucosa it was determined that genotype IL1β-511Т/Т is associated with the deeper local level of IL1β. Meanwhile the patients having erosive esophagitis had lover level of IL1β. It was determined that genotype IL1RN2/2 and haplotype IL1RN*2 /IL1В-31*Т are connected with the high risk of esophagus cancer of patients having Helicobacter pylori. Genotype IL1β-511Т/Т and haplotype IL1β-511Т/Т /IL1RN1/1 of the patients having GERD are associated with the low risk of the esophagus cancer. So, the allele IL1RN*2 and genotype IL1RN2/2 can combine by independent predictors of GERD progression. The study of this field should be continued taking into account not only changes in gastric mucosa, presence of helicobacteriosis, but also the nature of gastroesophageal reflux.

Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

Association of Polymorphisms in Inflammatory Cytokines Encoding Genes With Anti-N-methyl-D-Aspartate Receptor Encephalitis in the Southern Han Chinese

Background: Single nucleotide polymorphisms (SNPs) that occur within genes encoding inflammatory cytokines can result in quantitative or qualitative changes in their expression or functionality, potentially leading to the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. This study sought to evaluate the relationship between SNPs in inflammatory cytokines genes and the incidence of anti-NMDAR encephalitis in the Southern Han Chinese.Methods: In total, we enrolled 107 patients with anti-NMDAR encephalitis as well as 202 inpatient controls who had no first-degree relative with autoimmune diseases. Genotyping determination of all 309 patients was conducted for the IL-1β rs16944, IL-4 rs2243250, IL-4 rs2070874, IL-6 rs1800796, IL-10 rs1800872, and IL-17 rs2275913 gene SNPs.Results: We observed statistically significant differences in the frequencies of G allele in IL-1β rs16944 between anti-NMDAR encephalitis and controls (p = 0.017). Also, IL-1β, IL-4, IL-6, IL-10, and IL-17 SNPs were not associated with the disease (p > 0.05).Conclusions: We found that patients with anti-NMDAR encephalitis exhibit a distinct immunological profile, and we found that the decreased frequency of G allele in IL-1β rs16944 showed a protective role for anti-NMDAR encephalitis in the Southern Han Chinese.

Cytokine Polymorphisms and Predisposition to Diabetic Nephropathy: A Meta-Analysis

Background: Cytokine polymorphismsmight influence the predisposition to diabetic nephropathy (DN), but the results of already published related studies are still controversial and ambiguous. Objectives: The authors designed this meta-analysis to more precisely estimate relationships between TNF-α/IL-1/IL-4/IL-8/IL-18polymorphisms and DN by pooling the results of already published related studies. Methods: The authors searched Pubmed, Embase, Web of Science and CNKI for already published studies. Thirty already published studies were pooled and analyzed in this meta-analysis. Results: The overall pooled meta-analysis results showed that distributions of TNF-α –238 G/A, TNF-α –308 G/A, TNF-α –1031 C/T, IL-1A −889 C/T, IL-1B −511 C/Tand IL-18 –137 G/C polymorphisms among patients and controls differed significantly. Additionally, we also found that distributions of TNF-α –308 G/A, IL-1B −511 C/T and IL-18 –137 G/C polymorphisms among patients and controls from Asians differed significantly, and the distribution of the IL-1B −511 C/T polymorphism among patients and controls from Caucasians also differed significantly. Conclusion: The meta-analysis results demonstrated that TNF-α –238 G/A, TNF-α –308 G/A, TNF-α –1031 C/T, IL-1A −889 C/T, IL-1B −511 C/Tand IL-18 –137 G/Cpolymorphisms might influence predisposition to DN in the overall pooled population. Moreover, TNF-α –308 G/A, IL-1B −511 C/T and IL-18 –137 G/C polymorphisms might influence predisposition to DN in Asians, whereas the IL-1B −511 C/T polymorphism might also influence predisposition to DN in Caucasians.

A preliminary study of cytokine gene polymorphism effects on Saudi patients with colorectal cancer.

Objectives:To determine the possible associations of polymorphisms in interleukin (IL)-8 (rs4073 T/A), IL-10 (rs1800896 A/G), IL-22 (rs1179251 C/G and rs2227485 C/T), IL-27 (rs17855750 T/G), and transforming growth factor beta 1 (TGFß1) (rs1800469 C/T) with colorectal cancer (CRC) susceptibility in Saudi patients.Methods:The case-control study was carried out between July 2019 and January 2020 in King Khaled University Hospital, Riyadh, Saudi Arabia. A total of 70 patients with CRC and 70 healthy controls were included in the study. Single nucleotide polymorphisms of promoter regions were determined using TaqMan genotyping assays.Results:A statistically significant reduction in CRC risk was identified for carriers of the IL-10 (rs1800896 A/G) AG genotype, IL-22 (rs1179251 C/G) G allele, IL-27 (rs17855750 T/G) G allele and TGFß1 (rs1800469 C/T) CT and TT genotype. While IL-10 (rs1800896 A/G) AA genotype and TGFß1 (rs1800469 C/T) CC genotype were significantly associated with increased susceptibility to CRC. No significant associations were identified between the cytokine polymorphisms of IL-8 (rs4073 T/A) and IL-22 (rs2227485 C/T), and CRC risk.Conclusion:Our findings indicate a significant impact of IL-10 (rs1800896 A/G), IL-22 (rs1179251 C/G), IL-27 (rs17855750 T/G) and TGF-ß1 (rs1800469 C/T) polymorphisms on risk of CRC; while the IL-8 (rs4073 T/A) and IL-22 (rs2227485 C/T) and polymorphisms were not associated with CRC risk.

Genetic polymorphism of the infl ammatory cytokines IL-1β and IL-6 in patients with serologically identifi ed atrophic gastritis

Background : some researchers have demonstrated a link between the genetic polymorphism of certain pro-infl ammatory cytokines (IL-1β, IL-6) and the risk of developing precancerous diseases of the stomach and gastric cancer (GC). Aim : to study the genotypes and alleles frequency of polymorphisms of –511C/T (rs16944) of the IL1B gene and 174G/C (rs1800795) of the IL6 gene in patients with serologically detected atrophic gastritis (AG) — the main precancerous lesions of the stomach. Materials and methods . the study included 55 people (45 females and10 males) with an average age of 58.2 ± 11.5 years with signs of obvious or possible atrophy of diff erent parts of the gastric mucosa revealed by enzyme-linked immunosorbent assay (ELISA) with determination of pepsinogen levels I (PGI), PGII, the PGI / PGII ratio, gastrin-17 and IgG antibodies to H. pylori using the “GastroPanel” diagnostic kit (Biohit Plc, Helsinski, Finland). DNA was isolated from venous blood using the phenol-chloroform extraction method. DNA samples were genotyped according to published methods. Results : in patients with severe AG (PGI level less than 30 μg/l), the combined variant with the rare T allele (T/T + C/T) was detected signifi cantly more often (68.8%) than the common homozygous C/C variant (31, 3%, p = 0.004). In individuals with a low PGI/PGII ratio (less than 3), which is also evidence of fundamental atrophy, the homozygous T/T variant was more common (29.6%) than the C/C genotype (7.4%, p = 0.04) The average PGI values were signifi cantly lower with the C/C genotype of the IL-6 gene compared with the heterozygous C/G variant (p = 0.03), however, in patients with morphologically confi rmed atrophy, the combined variant with the rare G allele (G/G + C/G) of the IL6 gene was more common than the homozygous C/C variant (71.4% versus 28.6%, p = 001). Conclusions : in patients with signs of corpus atrophy (low PGI, PGI PGII ratios), the homozygous variant with a rare T allele, which is associated with increased IL-1β production and the development of a hypoacid state, was 4 times more likely than the homozygous C/C variant (p = 0.04). The results obtained suggest a possible association of IL1B polymorphism (carriage of a rare T allele) with the formation of a cancer phenotype of gastritis. The contribution of IL6 polymorphism requires further refi nement.

Genotype and Haplotype of Interleukin-17F (IL-17F) in Peptic Ulcer in Iraqi Patients

A peptic ulcer can be described as a condition in which there is a discontinuity in the entire thickness of thegastric mucosa. The discontinuity can also involve the submucosa, and in some cases, the deeper layers ofthe muscle wall(1). Immunological serological and molecular factors play a great role in the susceptibilityand diagnosis of this disease. IL-17F genotyping were reported to have an influencing in all types of pepticulcer. The current study aims to detect some cytokine concentration (proinflammatory and Regulatory) inpatients’ blood, and some cytokine polymorphism. During the time from July 2019 to November 2019,the case-control study enrolled 318 blood samples collected from the patients who attended the MarjanTeaching Hospital- Hilla, as well as 60 healthy people. IL-17F genotyping was performing for 55 patientswith peptic ulcer, and 30 healthy people as control, by using the PCR-SSP method. All types of peptic ulcerswere significantly associated with IL-17F. Associations were also observed with IL-12A and IL-CXCR2.In conclusion, IL-17F, haplotypes, and genotypes have related to peptic ulcers so it can be dependent as agenetic marker for the susceptibility of this disease in Iraq