Interleukin-10 Gene Polymorphisms Research Articles

Psoriasis: Association of interleukin-17 gene polymorphisms with severity and response to treatment.

Psoriasis is a chronic, inflammatory disease with a complex pathogenesis that is not yet fully understood. Although it is a multifactorial disease, the genetic factor has a major role in the pathogenesis of psoriasis. Genome wide association studies have identified over 50 genetic loci associated with psoriasis risk. Beside TNF-α or IL-23, the IL-17 family is a newer group that has proven implications in the pathogenesis of psoriasis. The most important members of the family, with pro-inflammatory qualities, are IL-17A and IL-17F. These interleukins are produced by a varied number of cells, but by far the most important are Th17 cells. Of the patients 20-30% present moderate-to-severe psoriasis, therefore, systemic medication (phototherapy, methotrexate, cyclosporine, acitretin or biologic agents) is mandatory. The necessity of an individualized treatment plan, for each patient, is imperative in order to establish the best strategy for non-responders to classical treatment or to other biologic treatments. The discovery of Th17 pathway improved the treatment and prognosis of psoriasis. Anti-psoriatic agents against IL-17 or its receptors are a novel group of biologic agents; these include ixekizumab, secukinumab and brodalumab. Polymorphisms of IL-17 family have been correlated with the severity and response to treatment in psoriasis, and also with the risk of inflammatory, infectious, autoimmune or neoplastic pathologies. The significant difference in the presence or absence of susceptibility loci in different population is due to genetic background and environmental factors that have a major impact on disease predisposition. In this study, we reviewed the importance and influence of the IL-17 polymorphisms as predictors of response to treatment and severity of the disease.

Association between interleukin-10 gene polymorphisms and severe chronic periodontitis.

Periodontitis is an inflammatory disease that is a result of the interaction between pathogenic bacteria and host immune response. Genetic alterations in interleukin-10 (IL-10) gene may be associated with the increased risk of periodontitis. We investigated the association between genotype and haplotype frequencies of IL-10 gene polymorphisms and susceptibility to periodontitis in an Iranian population. In this case-control study, a total of 64 patients with periodontitis and 128 healthy subjects were recruited. The PCR-RFLP technique was used to detect IL-10 promoter genotypes at the positions of -1082 (G/A), -819 (C/T), and -592 (C/A) in association with the susceptibility to severe chronic periodontitis. Regarding IL-10 -592 (C/A) and IL-10 -819 (C/T) alleles and genotypes, no significant association was observed between the risk of periodontitis and genotype frequencies. However, the frequency of GG genotype in IL-10 -1082 (G/A) polymorphic region was higher in normal subjects and was associated with the decreased risk of periodontitis under recessive model [OR=2.89, 95% CI (0.99-8.43), p=0.039]. Haplotype analysis revealed a significantly higher presence of H7 (AGC; -592/-1082/-819) [OR=97.74, 95% CI (95.52-99.96), p<0.0001]. IL-10 -1082(G/A) polymorphism and AGC (-592/-1082/-819) haplotype could be associated with the susceptibility to chronic periodontitis.

Genetic relationship between IL-10 gene polymorphisms and the risk of clinical atopic dermatitis

BackgroundWe retrieved different reports containing different genetic effects of − 1082 A/G, − 819 T/C, and − 592 A/C polymorphisms within the IL-10 (interleukin-10) gene on the susceptibility to clinical atopic dermatitis.MethodsHerein, we conducted a meta-analysis to comprehensively assess such a genetic relationship after collecting the available published evidence. STATA 12.0 software was used for the statistical analysis under the allelic, homozygotic, heterozygotic, dominant, recessive and carrier genetic models.ResultsBy retrieving and screening database literature, a total of 16 eligible case-control studies were finally selected. For the IL-10 -1082 A/G polymorphism, we did not detect a significant difference between atopic dermatitis cases and population-based controls in the overall meta-analysis under the genetic models of allele G vs. A (P = 0.540), GG vs. AA (P = 0.853), AG vs AA (P = 0.265), AG + GG vs AA (P = 0.221), GG vs AA+AG (P = 0.540) and carrier G vs. A (P = 0.643). Moreover, a statistically non-significant association was observed in the most subgroup meta-analyses by the factors of ethnicity, country and Hardy-Weinberg equilibrium. Likewise, the negative results were detected for the synthetic analysis of IL-10 -819 T/C and − 592 C/A polymorphisms.ConclusionThe current evidence does not support a strong genetic relationship between IL-10 -1082 A/G, − 819 T/C and − 592 A/C polymorphisms and the susceptibility to atopic dermatitis.

Interleukin-17 Gene Polymorphism Is Protective Against the Susceptibility to Adult Acute Myeloid Leukaemia in Egypt: A Case-Control Study.

BACKGROUND:Th17 cells are blamed for being accused in the pathogenesis of acute myeloid leukaemia. Th17 cells are CD4+ cell subtype. They produce IL-17A and IL-17F.AIM:This study aims to trace the relation between IL-17A and IL-17F polymorphisms and AML incidence and to define the connection between IL-17 polymorphisms and its serum level.METHODS:A group of 100 acute myeloid leukaemia patients and 100 age and sex-matched healthy subjects (controls) were enrolled in the present work. Restriction fragment length polymorphism- polymerase chain reaction (PCR-RFLP) was done to detect IL-17A (rs2275913; G197A) and IL-17F (rs763780; A7488G). Serum IL-17 level was assessed by Enzyme-linked immunosorbent assay analysis (ELISA) in both patients and controls.RESULTS:IL-17F, IL-17A mutant genotypes and alleles showed no significant relation with acute myeloid leukaemia incidence. Also, ELISA results proved that serum IL-17 did not vary between acute myeloid leukaemia patients and healthy subjects.CONCLUSION:Interleukin-17 gene polymorphisms did not consider a risk for acute myeloid leukaemia.

Interaction of polymorphism of the interleukin-6 gene with immunological damages and their role in the development of mixed cryoglobulinemia in patients with chronic hepatitis C

Aim. To determine the role of the relationship of immunological disorders with interleukin-6 gene polymorphism in the formation of HCV-associated mixed cryoglobulinemia. Materials and methods. The study included 149 patients with chronic hepatitis C. The polymorphism of the IL-6 gene (rs1800795) was determined by the method of polymerase chain reaction, the quantitative content of IL-6, RF IgM and IgG by enzyme immunoassay, cryoglobulins by spectrophotometric method. The patients were divided into groups depending on the polymorphism of the IL-6 gene and the presence of mixed cryoglobulinemia. Results. The frequency of formation of HCV-associated mixed cryoglobulinemia depended on the polymorphism of the IL-6 gene. In patients with chronic hepatitis C with mixed cryoglobulinemia, the frequency of registration of the CC genotype of the IL-6 gene was lower than in patients without mixed cryoglobulinemia, namely, in 9.7 % versus 28.6 % of patients. The presence of the G-allele, namely the CG/GG genotypes of the IL-6 gene polymorphism, was more often detected in patients with mixed cryoglobulinemia, namely, in 90.3 % of patients against 71.4 % of patients without signs of mixed cryoglobulinemia (χ 2 = 8.94, P = 0.003). In the presence of G-allele, the quantitative content of IL-6 inthe serum of the general group of patients with CHC was higher than in healthy people (P 0.05). The highest levels of IL-6 were recorded in patients with HCV-associated mixed cryoglobulinemia who had the G-allele. The content of IL-6 in the blood serum of these patients exceeded the indicators of both healthy people (P < 0.001) and the results of patients without mixed cryoglobulinemia (P < 0.01). In patients with chronic hepatitis C with mixed cryoglobulinemia, even in the presence of the CC genotype, the content of IL-6 in serum was higher both in comparison with healthy (P < 0.01) and in comparison with patients without signs of this extrahepatic manifestation (P < 0.01). In patients with chronic hepatitis C with mixed cryoglobulinemia, the presence of CG/GG genotypes was associated not only with the highest serum IL-6 content, but also with the presence of more pronounced autoimmune disorders due to a higher content of RF IgM (P = 0.04) and mixed cryoglobulins (P = 0.03) in serum, in comparison with patients who had the CC genotype. Moreover, the presence of more pronounced immune disorders in patients with HCV-associated mixed cryoglobulinemia in the presence of CG/GG genotypes was accompanied by more frequent manifestation of severe general weakness (P = 0.003), arthralgia (P = 0.02) and the formation of Meltzer’s triad. Conclusion. The frequency of detection of the G-allele, namely the CG/GG genotypes of the IL-6 gene polymorphism, is the highest in patients with HCV-associated mixed cryoglobulinemia (90.3 %). The presence of CG/GG genotypes in patients with chronic hepatitis C with mixed cryoglobulinemia contributes to more pronounced immunological disorders due to the highest content of IL-6, mixed cryoglobulins, and RF IgM in serum, which causes the manifestation of the clinical symptoms of this hepatic manifestation.

Identification and sequencing of periodontal-causing bacteria and its Relationship with Interleukin-6 Gene Polymorphism by Tetra-Arms-PCR

Identification and sequencing of periodontal-causing bacteria and its Relationship with Interleukin-6 Gene Polymorphism by Tetra-Arms-PCR

Interleukin gene polymorphisms in chronic periodontitis: A case-control study in the Indian population

ObjectiveThe aim of the present study was to investigate the possible association between seven Interleukin (IL) gene polymorphisms and their interaction with the chronic inflammatory oral disease, chronic periodontitis in Indian population. DesignA total of 357 study subjects (157 with chronic periodontitis and 200 with healthy control) were genotyped for IL1A -889C/T (rs1800587), IL1B -31C/T (rs1143627), IL1B -511A/G (rs16944), IL1B + 3954C/T (rs1143634), IL2 −330 T/G (rs2069762), IL4 -33C/T (rs2070874), IL6 −597 G/A (rs1800797), IL8 -251A/T (rs4073), IL10 -819C/T (rs1800871), IL10 -592A/C (rs1800872) and IL13 -1111C/T (rs1800925). Statistical analysis was performed using the statistical software package SPSS v16. SNPassoc and Multifactor Dimensionality Reduction algorithm v3.0.2. ResultsWe found that the statistically significant association of IL1A-889C/T (rs1800587), IL1B -31C/T (rs1143627), IL1B -511A/G (rs16944) and IL1B + 3954C/T (rs1143634) gene polymorphisms with increased susceptibility of chronic periodontitis. The best gene-gene interaction model was IL1B(-31C/T) X IL1B(+3954C/T) X IL10(-819C/T) with 10/10 cross validation consistency. The variant allele of IL1A, IL1B, IL10 and IL13 were seemed to be linked with chronic periodontitis increased susceptibility. The results of this study also indicate that epidemiological factors especially oral habits also play an important role in the development of chronic periodontitis. ConclusionsThis study concludes IL1A -889C/T (rs1800587), IL1B -31C/T (rs1143627), IL1B -511A/G (rs16944), IL1B + 3954C/T (rs1143634), IL10 -819C/T (rs1800871), IL10 -592A/C (rs1800872) and IL13 -1111C/T (rs1800925) gene polymorphisms are significantly associated with chronic periodontitis. This work also infers that the best interactive model comprised of IL1B and IL10 polymorphisms cumulatively increase the risk of chronic periodontitis.

Association of Interleukin 13/+110 Gene Polymorphism with Hepatitis B Virus Infection in Golestan Province, Northern Iran

Background: The most common primary cause of liver cancer is hepatocellular carcinoma (HCC). Cytokines as mediators have significant roles in immune and inflammatory responses. Interleukin-13 (IL-13) is a potent pleiotropic cytokine. Objectives: The aim of this study was to evaluate the association of IL-13/+110 gene polymorphism in patients with chronic hepatitis B virus (HBV), one of the most important factors that lead to the development of HCC. Methods: DNA was extracted from peripheral blood cells of all 585 participants including 302 unrelated Hepatitis B surface antigen (HBS-Ag) positives and 283 healthy matched groups. The IL-13 gene polymorphism (+ 110 A or G) was genotyped by SSP-PCR method and then genotype frequencies were checked by using the Pearson’s chi-square test and/or Fisher exact test. Results: The frequencies of A/G genotype (CI = 1.18 - 2.34, OR = 1.66, P = 0.004) and A/A genotype (CI = 0.95 - 3.53, OR = 1.84, P = 0.071) were higher in the patients. Also, the frequency of A allele was remarkably higher in the HBV patients than control group (CI = 1.09 - 1.79, OR = 1.84, P = 0.071). Conclusions: High frequency of A allele in patients rather than control group suggested that A allele probably plays a role in augmenting susceptibility to HBV infection risk and high frequency of G allele in controls suggested this allele has a protective role in this disease.

Investigation of Interleukin-17 Gene Polymorphisms and Serum Levels in Patients with Basal Cell Carcinoma of the Skin.

Interleukin 17 (IL-17) is a pro-inflammatory cytokine that plays an important role in cancer pathogenesis. To investigate the association of two IL-17 gene polymorphisms (rs2275913 and rs763780), as well as IL-17 serum levels with susceptibility to Basal Cell Carcinoma (BCC) of skin. Two hundred subjects with BCC and 200 healthy controls were recruited. DNA was extracted from peripheral blood leukocytes and genotypes were determined using PCR-RFLP methods. Serum levels were assessed by ELISA. At position rs2275913 in IL-17A, the frequencies of GG, AG and AA genotypes were 99 (49.5%), 76 (38%) and 25 (12.5%) in patients and 97 (48.5%), 84 (42%) and 19 (9.5%) in the control group. The distribution of AA, GA and GG genotypes at position rs763780 in IL-17F were 166 (83%), 34 (17%) and 0 (0%) in patients and 158 (79%), 40 (20%) and 2 (1%) in the control group. Haplotype analysis by Arlequin software package revealed that GA haplotype was the most frequent haplotype in both groups. No significant differences were found in alleles, genotypes, and haplotypes frequencies between study groups at both positions (P>0.05). While no difference in IL-17 serum levels was observed between individuals with different genotypes, statistical analysis showed higher IL-17A serum levels, but not IL-17F, in patients compared to controls (0.65 ± 0.11 and 0.03 ± 0.02 pg/ml), respectively, (P<0.001). Our findings do not support the association of rs763780 and rs2275913 gene polymorphisms in IL-17gene with susceptibility of Iranians with BCC. Increased IL-17A serum levels may still play a role in pathogenesis of BCC.

Association of interleukin-17 gene polymorphisms and susceptibility to brucellosis in Hamadan, western Iran.

IL-17is one of the most important inflammatory cytokines that stimulate immunity responses in humans infected with Brucella species, acting as a regulator that reduces release of γ-IFN, thus increasing resistance to brucellosis. Gene polymorphisms in the regulatory regions of cytokine-encoding genes affect the amountsof cytokines produced and play a fundamental role in infectious diseases. The aim of this study was to determine the association between IL-17 gene polymorphisms and susceptibility to brucellosis. In this case-control study, 86 patients with brucellosis and 86 healthy persons in Hamadan, western Iran, from September 2014 to September 2016, were included. IL-17 genetic variants at positions rs4711998 A/G, rs8193036 C/T, rs3819024 A/G, rs2275913 A/G, rs3819025 A/G, rs8193038 A/G, rs3804513 A/T, rs1974226 A/G and rs3748067 A/G were analyzed by restriction fragment length polymorphism-PCR. Serum IL-17 titers were measured by sandwich ELISA. GG genotypes at positions rs4711998 and rs3748067 were present significantly more frequently in patients with brucellosis than in controls (P < 0.05). The AA genotype at positions rs4711998, rs2275913 and rs3748067 and GG genotype at position rs19744226 were present significantly more frequently in controls than in the patient group. These results suggest that the AA genotype at positions rs3748067, rs3819025 and rs4711998 and GG genotype at position rs3819024 are likely protective factors against brucellosis, whereas the GG genotype at positions rs3748067, rs3819025 and rs4711998 and AA genotype at position rs3819024 may be risk factors against the disease. No significant relationships were found between serum IL-17 titers and genotypes of the single-nucleotide polymorphisms.

Novel Interleukin-10 Gene Polymorphism Is Linked to Gestational Diabetes in Taiwanese Population.

Objective: The association of interleukin-10 (IL-10) polymorphism with diabetes and its complication was recently established, while there were few researches considering the potential role of IL-10 in gestational diabetes (GDM). This study aimed to investigate the association between IL-10 gene rs1800896 (−1082 A/G), rs1800871 (−819 T/C), rs1800872 (−592 A/C), and rs3021094 (3388 A/C) single nucleotide polymorphisms (SNPs) and GDM susceptibility.Methods: This study included 72 GDM patients and 100 healthy pregnant women. Direct sequencing of the products from polymerase chain reactions of the extracted genomic DNA from study subjects were conducted for analyzing IL-10 gene polymorphism and further genotype frequencies were compared. Plasma IL-10 concentration was measured by ELISA method.Results: The results revealed no significant difference in −592 A/C, −819 T/C, and −1082 A/G genotypes. Significantly increased prevalence of A allele (P = 0.028, OR = 1.69, 95% CI = 1.081–2.64) and A/A genotype (P = 0.031, OR = 2.881, 95% CI = 1.145–7.250) at a previously un-characterized rs3021094 SNP were discovered in the GDM group. Increased IL-10 levels and insulin resistance were also related to the genotype of rs3021094. The risk of GDM was increased when IL-10 level was over 6.5 pg/ml.Conclusion: Our study demonstrated that A allele and A/A genotype of rs3021094 SNP in IL-10 gene were linked to increased risk for GDM, IL-10 plasma level and insulin resistance, which could be potential targets for early screening and detection of GDM.

Influence of interleukin-6 gene polymorphism on the efficacy of antiviral treatment in patients with chronic hepatitis C

Aim. The aim of the work was to determine the influence of interleukin-6 gene polymorphism on the effectiveness of antiviral therapy in patients with chronic hepatitis C. Materials and methods. A total of 83 patients with chronic hepatitis C (CHC). were included in the study. The efficacy of therapy with the peg-IFNα + SOF + RBV was analyzed depending on the polymorphism of interleukin-6 gene (rs1800795). Results. All CHC patients with the CC genotype (14 – 100 %) responded to antiviral therapy with the peg-IFNα + RBV + SOF, but only 85.5 % of the patients with CG/GG genotypes responded (59 of the 69). In CHC patients with CG/GG genotypes, who responded to the therapy by SVR 24 formation, the HCV-RNA negativization was slower, in contrast to patients with the CC genotype, who showed a persistent absence of the virus in the blood from the 4th week of treatment. All patients with the CC genotype of IL-6 gene polymorphism presented complete normalization of ALT activity at this time if SVR 24 had been achieved. In the vast majority of CHC patients with SVR 24 and the CG/GG genotype after the therapy cessation, ALT activity continued to decrease and normalized after 24 weeks of observation in 94.9 % (56 of the 59). However, 20.0 % of patients with the CG/GG genotype who did not respond with the formation of SVR 24, had elevated serum ALT activity at the time of SVR 24 evaluation. Kendall’s rank correlation was performed to determine the factors, which statistically significantly affect the results of peg-IFNα + RBV + SOF therapy. IL-6 gene polymorphism had an effect on the efficacy of therapy, both on the HCV-RNA negativization in the blood at the end of treatment (P = 0.04) and on the achievement of SVR 24 (P = 0.03). The lack of response as well as the lack of SVR 12 and SVR 24 formation at the time of therapy completion were associated with the IL-6 gene CG/GG polymorphism presence and a higher index of ALT activity at the beginning of treatment (τ = -0,18, P < 0.01). Conclusions . In CHC patients, the CC genotype of IL-6 gene (rs1800795) is a favorable prognostic factor for the formation of SVR24 in the treatment of peg-IFNα + RBV + SOF. Patients who did not respond to the treatment by SVR 24 formation had only the IL-6 gene CG/GG polymorphism. Even in HCV patients with CG/GG genotypes who responded to the treatment by SVR 24 formation, the negativization of HCV-RNA in the blood was slower, unlike the patients with CC genotype. The absence of response at the time of therapy completion, as well as the absence of SVR 12 and SVR 24, were associated with the presence of the IL-6 gene CG/GG polymorphism and a higher level of ALT activity at the beginning of therapy (τ = -0,18, P < 0.01).

Correlations of IL-17 and NF-κB gene polymorphisms with susceptibility and prognosis in acute respiratory distress syndrome in a chinese population.

The present study was performed to investigate the association between interleukin-17 (IL-17) and nuclear factor κB (NF-κB) gene polymorphisms and the risk and prognosis of acute respiratory distress syndrome (ARDS) in a Chinese population. A total of 210 Chinese patients with ARDS were selected as the study group, 210 individuals who were identified as at-risk patients but did not meet criteria for ARDS were recruited as the control group. Three single nucleotide polymorphisms (SNPs) of IL-17, including rs763780 (A>G), rs2275913 (G>A), rs8193036 (C>T) and NF-κB1 gene rs3774934 (G>A) loci were examined by Sanger sequencing technique in the peripheral blood of all subjects. Patients were followed for 30-day survival. The IL-17 rs763780 and NF-κB1 rs3774934 SNPs had no impact on ARDS risk and prognosis of ARDS (P>0.05). Compared with individuals carrying the wild-type GG genotype of rs2275913 at IL-17, the AA-homozygous and GA- heterozygous individuals were protected from the development of ARDS. Consistently, a decreased 30-day mortality risk was found among A-allele carriers of rs2275913 at IL-17 (p<0.05). For IL-17 rs8193036 SNP, the homozygote TT genotype and heterozygote CT genotypes were associated with increased ARDS susceptibility and 30-day mortality risk (P<0.05). Besides, decreased IL-17 levels were found in A-allele carriers of IL-17 rs2275913, whereas individuals carrying T-allele of IL-17 rs8193036 were found to have significantly increased levels of IL-17 (P<0.05). Our results suggested that two functional polymorphisms of IL-17, rs2275913 and rs8193036 were associated with ARDS risk and prognosis, indicating that the two genetic variants might act as possible markers for the prediction of ARDS risk and development.

Assessment of Interleukin-18 gene polymorphism and serum levels in oral lichen planus in an Indian population.

Oral lichen planus (OLP) is a chronic, inflammatory disease with uncertain etiology. The aim of this study was to assess Interleukin-18 (IL-18) gene polymorphism and serum levels in OLP cases of Indian origin and to compare them with a control population of similar background. The assessment of single-nucleotide polymorphisms (SNPs) of IL-18 gene at promoter regions -137(G/C) and -607(C/A) was done in 70 OLP cases and 70 healthy controls using sequence-specific primer-polymerase chain reaction (SSP-PCR). In a subset of this cohort, comprising of 41 OLP cases and 41 controls, serum IL-18 levels were assessed using enzyme-linked immunosorbent assay (ELISA). Mean serum levels of IL-18 among OLP cases were significantly higher when compared to controls. Genotypic and allelic frequencies of IL-18 at position -137(G/C) showed that GG genotype and allele G was significantly higher in OLP cases, whereas, GC genotype and C allele was high in the control group. Polymorphism of IL-18 at position -607(C/A) showed no significant differences. Gene polymorphism at -137GG genotype and allele G seems to be associated with genetic susceptibility to OLP whereas -137GC and allele C may have a protective role against its development. However, our study lacks clear statistical correlation, the differences observed could be caused by sampling problems and the results could not be fully representative of Indian patients with OLP. Further studies are warranted to explore the role of IL-18 genetic polymorphisms in OLP development.

IL18 Gene Polymorphism Influences Age of Onset of DM1 in African Ancestry Brazilians.

The aim of this study was to investigate the relationship of two single nucleotide polymorphisms (SNPs) in the interleukin-18 ( IL18 ) gene (rs187238, g.-137G > C; rs1946518, g.-607C > A) and one SNP of the IL12B gene (rs3212227 g.*159A > C, 3'UTR) with the age of onset for type 1 diabetes mellitus (DM1). A total of 1,101 patients with DM1 enrolled in 13 centers from different regions of Brazil were genotyped with TaqMan assay and classified according to the ancestry. Our results show that an SNP in IL18 gene could be associated with DM1 age onset, taking into account that this studied variation affects gene expression.

Correlation between Interleukin-17 gene polymorphism and osteoarthritis susceptibility in Han Chinese population

BackgroundInterleukin-17 (IL-17), a pleiotropic cytokine, plays a significant role in the inflammatory diseases. By a pilot study with small population, IL-17 polymorphisms (IL-17A rs2275913 and IL-17F rs763780) showed a more potential risk factor in knee osteoarthritis (OA) in our recruited subjects. In the current study, the association between IL-17A rs2275913 and IL-17F rs763780and the risk of OA in a Chinese population is studied.MethodsThe IL-17A rs2275913 and IL-17F rs763780 polymorphisms were determined in 594 knee OA cases and 576 healthy controls, using polymerase chain reaction-restriction fragment length polymorphism assay. The relationship between genotype distribution and disease risk, as well as OA severity was analyzed by Chi-square test and multivariate logistic regression.ResultsThe experimental results indicated that the polymorphism in IL-17 gene rs2275913 site were related to knee OA risk after the adjustment of BMI, sex, age, smoking and drinking status (AA vs. GG: odds ratio (OR), 1.411; 95% confidence interval (CI), 1.021–1.950; P = 0.040; A allele vs. G allele: OR, 1.192; P = 0.037; 95% CI, 1.012–1.404;). Similarly, subjects who are bearing the rs763780 variant genotypes (TC and CC) and C allele also had a higher susceptibility to knee OA compared with those who are bearing the TT genotype (TC vs. TT, OR: 1.312; P = 0.039; 95% CI: 1.017–1.692; CC vs. TT, OR: 2.812, P = 0.006, 95% CI: 1.338–5.909; C allele Vs. T allele, OR:1.413, P = 0.002, 95% CI:1.141–1.751). In the meantime, one high-risk haplotypes, AC (OR was 7.22, P < 0.01) was found. Both two polymorphisms do not correlated with OA severity based on Kellgren-Lawrence (K&L) scales. Finally, serum IL-17 levels of knee OA patients were greatly higher than those of controls (P = 0.001).ConclusionsWith the limited size sample, our study shows that IL-17 gene polymorphisms possibly related to the high-risk knee OA occurrence.

Association between interleukin-18 (137G/C and 607C/A) gene polymorphisms and risk of ischemic stroke

Over the years, numerous researchers have explored the relationship between ischemic stroke (IS) and interleukin-18 (IL-18) gene polymorphisms. However, those studies reported conflicting and ambiguous results. The effects of IL-18 (137G/C and 607C/A) genetic variants on IS were investigated in this article. We performed a systematic search that was comprehensively executed in online databases for studies published up to 30 April 2018. Calculation of pooled odds ratios (ORs) and 95% confidence intervals was applied to assess the intensity of correlation using Stata.12.0. The overall outcome showed that 137G allele increased the risk of IS under the homozygous model (OR=1.36, P=0.027). Nevertheless, on the basis of ethnicity for the subgroup analysis (Asian and Egyptian), it was disclosed that the association was only found in the Egyptian population under the allelic model (OR=2.72, P=0.001) and recessive model (OR=5.04, P=0.000). In the overall analysis, 607C allele increased the risk of IS under all hereditary models (C vs. A: OR=1.26, P=0.002; CC vs. AA: OR=1.67, P=0.002; CA vs. AA: OR=1.30, P=0.001; CC+CA vs. AA: OR=1.41, P=0.000; CC vs. AA+CA: OR=1.48, P=0.000); a similar trend was observed in the Asian population. However, 607C allele was linked to decreased IS risk in the Egyptian population under all genetic models except the heterozygous model (C vs. A: OR=0.48, P=0.006; CC vs. AA: OR=0.19, P=0.007; CA vs. AA: OR=0.47, P=0.078; CC+CA vs. AA: OR=0.39, P=0.020; CC vs. AA+CA:OR=0.30, P=0.030). Although two polymorphisms were associated with IS, the association varied significantly in different countries. Large epidemiological studies will be required to verify these findings in the future.

Association Between Interleukin-33 Polymorphism and Henoch-Schönlein Purpura in Chinese Children

Objectives: Interleukin-33 (IL-33) was one of the members of IL-1 family, and it was reported that the single nucleotide polymorphisms (SNPs) in the IL-33 gene was contribute to the susceptibility to immune related diseases, including rheumatoid arthritis, asthma, Behcet’s disease, systemic lupus erythematosus and ankylosing spondylitis. However, the potential association between SNPs in IL-33 gene and Henoch-Schonlein purpura (HSP) was not explored. Methods: We designed a case-control study, a total of 181 HSP patients and 202 healthy pediatric controls were included, which aimed to study the relationship between the SNPs in the IL-33 gene (rs1929992, rs7044343) and HSP with a Chinese pediatric cohort. Results: There were no evidence for the association of rs1929992 and rs7044343 polymorphism in IL-33 gene with pediatric HSP patients (C versus T, P = 0.622, OR = 0.931, 95% CI: 0.7 - 1.238; TT versus CC, P = 0.742, OR = 0.908, 95% CI: 0.513 - 1.609; CT versus CC, P = 0.158, OR = 0.714, 95% CI: 0.446 - 1.141 and C versus T, P = 0.920, OR = 0.986, 95% CI: 0.742 - 1.309; TT versus CC, P = 0.939, OR = 0.978, 95% CI: 0.549 - 1.741; CT versus CC, P = 0.416, OR = 0.817, 95% CI: 0.501 - 1.331, respectively). Moreover, association studies were performed on the correlation between IL-33 gene polymorphisms and HSP nephritis patients as well as patients with gastrointestinal manifestation and joint involvement. However, there were no significant association regarding the distribution of allele and genotype frequencies between HSP patients with different system involvement and healthy controls either. Conclusions: The present findings indicated that both of rs1929992 and rs7044343 in gene IL-33 polymorphism were not related to the susceptibility to HSP and the different system involvement of HSP patients.

Association of Methylenetetrahydrofolate Reductase, Vitamin D Receptor, and Interleukin-16 Gene Polymorphisms With Renal Cell Carcinoma Risk.

In this meta-analysis, we investigated the association of methylenetetrahydrofolate reductase, vitamin D receptor, and interleukin-16 gene polymorphisms with the risk of renal cell carcinoma. We searched the PubMed and Cochrane Library databases up to July 1, 2017, and included 12 eligible case–control studies in our analysis. The vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype were all associated with the risk of renal cell carcinoma in Asian populations. However, methylenetetrahydrofolate reductase (rs1801133 and rs1801131), vitamin D receptor (TaqI and Fok1), and interleukin-16 (rs4778889 and rs11556218) gene polymorphisms were not associated with the risk of renal cell carcinoma. Our study indicates that the vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype are associated with renal cell carcinoma risk.

The significance of interleukin 4 (IL-4) (590-C/T) gene polymorphism in Iraqi patients with type 2 diabetes mellitus: A case-control study

One of well knows ant-inflammatory cytokines is Interleukin 4 (IL-4). It plays major roles in the control of immune responses at various levels. It is involved in the proliferation of activated B and T cells, inhibition of type 1 T helper differentiation, and promotion of type 2 T helper cell differentiation, control of B cell maturation (10-13). Moreover, it is involved in the growth, apoptosis, proliferation, and maturation of other hemopoietic and nonhemopoietic cells (14). Previous studies have investigated its role in allergic and autoimmune disorders (14-17). The gene for IL-4 is located at chromosome 5 within the long arm and possesses four exons (18). Several authors have shown a possible association of IL-4 gene polymorphism to a number of clinical disorders such as multiple sclerosis, atopic dermatitis, rheumatoid arthritis, and asthma (19-21). IL- 4 gene polymorphism has been linked to type 1 diabetes mellitus, but we in the current study aimed at investigating the significance of IL-4 590C/T (rs2243250) gene polymorphism in relation to type 2 diabetes and its long term complications. This study was aimed to assess the significance of IL-4 590C/T (rs2243250) gene polymorphism in relation to type 2 diabetes and its long term complications. The present case-control study was carried out at the diabetes center in Al-Diwaniayh Teaching Hospital, Al-Diwaniyah Province, Iraq. The study started in January 2019 and ended on July 2019. The study included 32 types 2 diabetes mellitus patients and 47 apparently healthy control subjects. Five ml sample of venous blood (antecubital vein) was obtained for the purpose of PCR analysis of IL-4 (590-C/T) gene polymorphism. The results of currents study revealed that the distribution of patients with type 2 diabetes was 21 (65.6 %), 9 (28.1 %) and 2 (6.3 %) as CC, CT, and TT genotypes; whereas, the distribution of control subjects was 33 (70.2 %), 10 (21.3 %) and 4 (8.4 %), as CC, CT, and TT genotypes. There was no significant difference in the frequency distribution of diabetic patients and control subjects according to IL- 4rs2243250 genotype (P = 0.757). IL- 4rs2243250 genotype polymorphism was not significantly correlated to retinopathy, nephropathy, neuropathy, CVA, IHD and dyslipidemia (P > 0.05), IL-4 IL- 4rs2243250 genotype polymorphism is neither associated with type 2 diabetes mellitus nor is linked to its long term microvascular and or macrovascular complications.