Association Of Cytokine Gene Polymorphisms Research Articles

Association of Cytokine Gene Polymorphisms and Their Impact on Active and Latent Tuberculosis in Brazil's Amazon Region.

Some genetic variations in cytokine genes can alter their expression and influence the evolution of Mycobacterium tuberculosis (Mtb) infection. This study aimed to investigate the association of polymorphisms in cytokine genes and variability in plasma levels of cytokines with the development of tuberculosis (TB) and latent tuberculosis infection (LTBI). Blood samples from 245 patients with TB, 80 with LTBI, and healthy controls (n = 100) were included. Genotyping of the IFNG +874A/T, IL6 -174G/C, IL4 -590C/T, and IL10 -1082A/G polymorphisms was performed by real-time PCR, and cytokine levels were determined by flow cytometry. Higher frequencies of genotypes AA (IFNG +874A/T), GG (IL6 -174G/C), TT (IL4 -590C/T), and GG (IL10 -1082A/G) were associated with an increased risk of TB compared to that of LTBI (p = 0.0027; p = 0.0557; p = 0.0286; p = 0.0361, respectively) and the control (p = <0.0001, p = 0.0021; p = 0.01655; p = 0.0132, respectively). In combination, the A allele for IFNG +874A/T and the T allele for IL4 -590C/T were associated with a higher chance of TB (p = 0.0080; OR = 2.753 and p < 0.0001; OR = 3.273, respectively). The TB group had lower levels of IFN-γ and higher concentrations of IL-6, IL-4, and IL-10. Cytokine levels were different between the genotypes based on the polymorphisms investigated (p < 0.05). The genotype and wild-type allele for IFNG +874A/T and the genotype and polymorphic allele for IL4 -590C/T appear to be more relevant in the context of Mtb infection, which has been associated with the development of TB among individuals infected by the bacillus and with susceptibility to active infection but not with susceptibility to latent infection.

Association of cytokine gene polymorphisms with peripheral neuropathy susceptibility in people living with HIV in Greece.

Relatively little research has been done in recent years to understand what leads to the unceasingly high rates of HIV sensory neuropathy despite successful antiretroviral treatment. In vivo and in vitro studies demonstrate neuronal damage induced by HIV and increasingly identified ART neurotoxicity involving mitochondrial dysfunction and innate immune system activation in peripheral nerves, ultimately all pathways resulting in enhanced pro-inflammatory cytokine secretion. Furthermore, many infectious/autoimmune/malignant diseases are influenced by the production-profile of pro-inflammatory and anti-inflammatory cytokines, due to inter-individual allelic polymorphism within cytokine gene regulatory regions. Associations of cytokine gene polymorphisms are investigated with the aim of identifying potential genetic markers for susceptibility to HIV peripheral neuropathy including ART-dependent toxic neuropathy. One hundred seventy-one people living with HIV in Northern Greece, divided into two sub-groups according to the presence/absence of peripheral neuropathy, were studied over a 5-year period. Diagnosis was based on the Brief Peripheral Neuropathy Screening. Cytokine genotyping was performed by sequence-specific primer-polymerase chain reaction. Present study findings identify age as an important risk factor (p < 0.01) and support the idea that cytokine gene polymorphisms are at least involved in HIV peripheral-neuropathy pathogenesis. Specifically, carriers of IL1a-889/rs1800587 TT genotype and IL4-1098/rs2243250 GG genotype disclosed greater relative risk for developing HIV peripheral neuropathy (OR: 2.9 and 7.7 respectively), while conversely, carriers of IL2+166/rs2069763 TT genotype yielded lower probability (OR: 3.1), all however, with marginal statistical significance. The latter, if confirmed in a larger Greek population cohort, may offer in the future novel genetic markers to identify susceptibility, while it remains significant that further ethnicity-oriented studies continue to be conducted in a similar pursuit.

The association of cytokine gene polymorphisms with tuberculosis susceptibility in several regional populations.

By collecting the data of all relevant articles, the goal of this study was to better understand the relationship between the IL-6/IL-18 polymorphism and susceptibility to tuberculosis in several regional populations. Pubmed, Embase, WOS and CNKI were used to find relevant literature. The findings of separate research were merged using Review Manager. A total of 25 studies were included in this study. IL-6 rs1800795 (dominant. comparison: p-value<0.0001, OR 1.43, 95 % CI 1.23-1.67; recessive comparison: p-value<0.0001, OR 0.48, 95 % CI 0.35-0.65; allele comparison: p-value<0.0001, OR 1.43, 95 % CI 1.27-1.62), IL-18 rs1946518 (dominant comparison: p-value=0.01, OR 1.19, 95 % CI 1.04-1.35; recessive comparison: p-value=0.01, OR 0.82, 95 % CI 0.71-0.96; allele comparison: p-value=0.002, OR 1.14, 95 % CI 1.05-1.24), IL-18 rs187238 (dominant comparison: p-value=0.0002, OR 1.35, 95 % CI 1.15-1.58; allele comparison: p-value<0.0001, OR 1.31, 95 % CI 1.14-1.50). All gene polymorphisms were shown to be substantially linked to tuberculosis in the general population. Positive findings of rs187238 and rs1800795 polymorphisms were primarily driven by several regional populations, according to subgroup analyses. This meta-analysis found that the the IL-6 rs1800795and IL-18 rs187238 polymorphisms may have a role in TB susceptibility.

High-resolution melting PCR analysis for genotyping the gene polymorphism of TNF-α, TGF-β1, IL-10, and IFN-γ in lung transplant recipients

High-resolution melting (HRM) analysis is a genotyping method which has the advantages of simple, rapid, low-cost and closed-tube operation.This study evaluated HRM analysis as an option for detecting the single nucleotide polymorphism (SNP) of cytokine, and profiled the distribution of cytokine gene polymorphism in the lung transplant recipients (LTRs).High-resolution melting-polymerase chain reaction (HRM-PCR) assays for genotyping tumor necrosis factor alpha (TNF-α) (-308 A/G), tumor growth factor beta 1 (TGF-β1) (+869 T/C), interleukin 10 (IL-10) (-592 C/A, -819 T/C, -1082 G/A), and interferon gamma (IFN-γ) (+874 T/A) SNPs were developed on the LightCycler® 480. The SNPs of the aforementioned cytokine genes in 322 LTRs and 266 normal controls were detected using HRM-PCR approach. To confirm the accuracy of the HRM-PCR assay, we randomly selected 100 samples from the LTRs and detected the aforementioned SNPs with sequence-specific primer-polymerase chain reaction (SSP-PCR) method, using a commercial kit.The data show that the HRM-PCR assay can distinguish all the cytokine SNPs, and the results of HRM-PCR analysis are in complete concordance to the genotyping results obtained using a commercial kit (κ = 1.0). Our data also show that the allele and genotype frequencies of the abovementioned cytokine are not significantly different between the LTRs and the control groups (p > 0.05). In addition, we found the genotypes of TGF-β1 +869 associated with high expression phenotype were prevalent in the LTRs. On the contrary, for TNF-α -308, IL-10 and IFN-γ, the genotypes associated with low expression phenotype were most common in the LTRs.In this study, we described a rapid, low-cost and high-throughput HRM-PCR technology for genotyping cytokine SNPs. Our data may be utilized for future studies examining the associations of cytokine gene polymorphisms with the prognosis of the LTRs.

Association of Cytokine Gene Polymorphisms with Prostate Cancer Risk from a Study in Central China.

Our study intended to investigate five cytokine gene single nucleotide polymorphisms (SNPs) and their associations with prostate cancer risk. Genotypes of five cytokine gene SNPs were detected by MassARRAY for blood samples from a group of patients with prostate cancer (n = 90) and a control group (n = 140) in central China. The differences in tumor clinical stages, Gleason scores, and PSA values in patients with prostate cancer were also investigated. The frequencies of the five cytokine gene SNPs (L-1β rs16944, IL-4 rs2070874, IL-4rs2227284, IL-16 rs7175701, and IL-16 rs11556218) genotypes were not found to be significantly mutated in prostate cancer patients compared with the control group. In addition, for five cytokine gene SNPs genotypic comparisons, patients with different Gleason scores, clinical stages, and PSA values were grouped into two subgroups. There was also no statistically significant association in all these subgroups. Our study suggests that cytokine gene polymorphisms may not be a risk factor for prostate cancer in a central Chinese population. Nevertheless, more large-scale studies on the Chinese population are necessary to examine our conclusions. The discovery of cytokine gene polymorphisms related to prostate cancer could update our understanding of the etiology and improve our knowledge of the early detection, diagnosis, and treatment of prostate cancer.

A Triad Study in South Indian Population of Telangana: On the Association of Cytokine Gene Polymorphisms in the Aetiology of Spontaneous Abortions

A Triad Study in South Indian Population of Telangana: On the Association of Cytokine Gene Polymorphisms in the Aetiology of Spontaneous Abortions

Association of cytokine gene polymorphisms with chronic hepatitis C virus genotype 1b infection in Chinese Han population: An observational study.

Cytokines are extensively involved in the process of hepatitis C virus (HCV) infection and take a crucial part in host immune regulation. We aimed to explore the potential correlation of cytokine single nucleotide polymorphisms (SNPs) with HCV susceptibility and response rate of interferon (IFN)-based antiviral therapy in Chinese Han population.A case–control genetic association study was conducted between 198 patients with chronic HCV genotype 1b infection and 142 healthy controls. Genetic polymorphisms of TNF-α (rs1800629), TGF-β (rs1800469), IL-10 (rs1800896, rs1800871, and rs1800872), IL-6 (rs1800795, rs1800796), IFN-γ (rs2430561), and IL-28B (rs12979860, rs12980275, and rs8099917) were analyzed by MassARRAY SNP technology. Patients were treated with IFNα-2b or pegylated-IFNα-2a plus ribavirin for 48 weeks. Sustained virological response (SVR) was assessed 6 months after the completion of the treatment.The IL-28B rs12979860-CC (odds ratio [OR] = 4.35, 95% confidence interval [CI]: 1.69–11.21, P = .001), rs12980275-AA (OR = 3.41, 95% CI: 1.08–10.76, P = .028), and rs8099917-TT (OR = 3.86, 95% CI: 1.49–10.12, P = .004) were significantly associated with SVR, and IL-10 rs1800871-TT (OR = .50, 95% CI: 0.25–1.00, P = .049) and rs1800872-AA (OR = .50, 95% CI: 0.25–1.00, P = .049) were also significant for SVR. No association was found between the cytokine SNPs and HCV susceptibility. Additionally, multivariate analysis showed that low baseline viral load (OR = 3.63, 95% CI: 1.01–13.02, P = .048), pegylated-IFN (OR = 9.68, 95% CI: 1.14–82.13, P = .037) and rs12979860-CC (OR = 6.08, 95% CI: 2.00–18.46, P = .001) were independent factors for SVR.IL-28 and IL-10 gene polymorphisms played an important role in predicting host response to IFN-based antiviral therapy in HCV genotype 1b infection.

Association of cytokine gene polymorphisms with susceptibility to cutaneous leishmaniasis in a Turkish population.

The objective of this study was to determine the association of TNF-α -308 G/A, IFN-γ +874T/A, IL-12B+1188 A/C, IL-10 -1082 G/A and IL-4 -590 C/T polymorphisms with susceptibility to CL. A total of 55 CL patients and 110 controls from Sanlıurfa province of Turkey were included to this study. Polymorphisms were genotyped by 'polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)' and 'amplification refractory mutation system-PCR (ARMS-PCR)' methods. A statistically significant difference was noted in the allele (P<.001, P=.002) and genotype (P<.001, P=.001,) frequencies of TNF-α -308 G/A and IL-4 -590 C/T, respectively. TNF-α 308 GG versus GA genotype (OR=19.556 [95% CI 8.310-46.019] P<.001), GG versus GA+AA genotype (OR=20.444 [95% CI 8.707-48.004] P<.001) and G versus A allele (OR=6.968 [95% CI 3.903-12.440] P<.001) revealed significant association with CL. IL-4 -590 CC versus TT+CT genotype (OR=2.049 [95% CI 1.025-4.096], P=.041) and C versus T allele (OR=2.441 [95% CI 1.355-4.396], P=.002) revealed significant association with CL. Our study indicates that TNF-α 308 G/A and IL-4-590 C/T polymorphisms are significantly associated with susceptibility to CL. Individuals carrying A allele at TNF-α promoter -308 position and T allele at IL-4 promoter -590 position are at a higher risk for CL.

Association of cytokine gene polymorphisms with osteoarthritis susceptibility.

Osteoarthritis (OA) is a multifactorial disease characterized by low-grade inflammatory processes that are mediated initially by the cells and factors of the innate immune system. In addition to their key role in inflammation, cytokines contribute to the pathogenesis of OA through angiogenesis and chemotaxis. The purpose of the present case-control study was to investigate a possible association of four cytokine single nucleotide polymorphisms (SNPs), IL-4R -3223C>T (rs2057768), IL-8 -251T>A (rs4073), IL-10 -1082A>G (rs1800896) and TNF -A-308G>A (rs1800629) with OA susceptibility. Genomic DNA was isolated from blood samples collected from 305 Romanian subjects (90 patients with OA and 215 controls) and the genotyping of the SNPs was performed by TaqMan allelic discrimination polymerase chain reaction using predesigned assays. Our data indicated a significant association for IL-4R rs2057768 C>T SNP. The subjects that carried the CT genotype were at a higher risk for OA (OR 2.03, 95% CI: 1.21-3.42, P=0.007) compared with those that had the CC genotype. Furthermore, the carriers of the T allele were at a 1.9 fold higher risk for OA (OR 1.92; 95% CI, 1.17-3.17; P=0.009) in a dominant model. The association remained significant only for knee OA in the subgroups analysis. No correlations were observed between the other remaining SNPs and OA. The results suggested that the IL-4R rs2057768 SNP could contribute to OA susceptibility in the Romanian population, providing novel evidence for the involvement of IL-4/IL-4R pair in the pathogenesis of OA.

Association of cytokine gene polymorphisms with bronchopulmonary dysplasia in Han Chinese newborns.

To investigate the association of 14 cytokine gene polymorphisms with bronchopulmonary dysplasia (BPD) among Han Chinese newborns. The 14 polymorphisms investigated were IL18 rs1946519, rs1946518, rs187238, rs360718, and rs360717 polymorphisms, IL10 rs3024493 polymorphism, IL6 rs1800795, rs1800796, and rs1800797 polymorphisms, TNF rs361525 and rs1800629 polymorphisms, and TGFB1 rs1800469, rs1800468, and rs1800471 polymorphisms. The polymorphisms could be associated with the risk of BPD among Han Chinese newborns. This is a retrospective study. Genotyping of these polymorphisms were performed on BPD cases (N = 1022) and non-BPD controls (N = 1039) who were ascertained using the established Jobe and Bancalari criteria. The odds ratios (ORs) of polymorphisms whose genotype distribution in the controls fulfilled the Hardy-Weinberg equilibrium (HWE) were calculated to evaluate the strengths of genetic association. Genotype distributions of IL6 rs1800795 and rs1800797 polymorphisms deviated significantly from HWE and were omitted from the analysis. Among the 12 remaining polymorphisms, only TNF rs361525 polymorphism demonstrated a statistically significant association with BPD risk. The heterozygous GA genotype of TNF rs361525 polymorphism showed an OR of 1.932 (1.512-2.470), while the homozygous AA variant genotype showed an OR of 2.927 (1.216-7.048) (P = 0.000 and P = 0.017, respectively). Besides, the allelic OR was also analyzed, and it was found that the variant A allele of TNF rs361525 polymorphism showed an OR of 2.146 (1.718-2.680) (P = 0.000). TNF rs361525 polymorphism could influence BPD risk among Han Chinese newborns.

Attention-Deficit/Hyperactivity Disorder And Inflammation: What Does Current Knowledge Tell Us? A Systematic Review.

Attention-deficit/hyperactivity disorder (ADHD) is a complex condition that interferes with development and/or functioning. Our objective is to investigate the potential association between ADHD and inflammation. We conducted a systematic review of human studies measuring inflammatory markers in ADHD. The studies were identified by searching PUBMED, MEDLINE, EMBASE, PSYCHINFO, COCHRANE, and SCOPUS databases for peer-reviewed journals published until September 2016. We included cytokine gene expression and protein measured. Fourteen papers met the inclusion criteria. Seven studies evaluated the association of cytokine gene polymorphisms in ADHD, and six studies measured cytokines levels in blood. One study analyzed the presence of cytokines in cerebrospinal fluid in patients with ADHD. Altogether, these studies indicate a possible role of inflammation in ADHD pathogenesis, despite the significant heterogeneity and contradictory results. Evidence points to the association of ADHD with inflammatory processes, but more studies are warranted.

Association of cytokine gene polymorphisms with the complications of allogeneic haematopoietic stem cell transplantation

The purpose of our study was to confirm the prevalence of the association between single nucleotide polymorphisms present in genes encoding cytokines and the complications occurring after haematopoietic stem cell transplantation (HSCT). 108 recipients and 81 donors were typed for TNF-α (−308), TGF-β1 (codon 10, 25), IL-10 (−1082, −819, −592), IL-6 (−174) and INF-γ (+874). Our studies have shown a tendency toward association between the occurrence of acute form of graft versus host disease (aGVHD) and IL-6 genotype. Homozygote C/C was less likely to develop aGVHD (p=0,09). Genotype GCC/ATA in IL-10 recipient gene alone had protective effect against the occurrence of aGVHD (p=0,01). Furthermore, GCC/ATA protected the host against developing the disease in the clinically relevant grades (II-IV) (p=0,03). In addition, the recipient’s T/T G/G genotype (TGF-β1) predisposed to the development of both acute (p=0,06 – trend) and chronic (p=0,04) GVHD and also severe aGVHD (p=0,004). We also observed a statistically significant association between the genotype of recipient and the risk of infection – the protective function of the G/C IL-6 in the bloodstream infections (p=0,001). Our results suggest that IL-6, IL-10 and TGF-β1 genotypes of recipient are the most associated with the risk of complications after HSCT.

Association of cytokine gene polymorphisms and risk factors with otitis media proneness in children.

In order to assess the association between gene polymorphisms and otitis media (OM) proneness, tumor necrosis factor alpha (TNFA) -308, interleukin (IL) 10-1082 and -3575, IL6 -597, IL2 -330, and CD14 -159 genotyping was performed in 58 OM-prone children and 85 controls who were exposed to similar number and frequency of environmental and host risk factors. The frequencies of genotypes (wild type vs. genotypes containing at least one polymorphic allele) were not significantly different between groups, except for IL10 -1082. Polymorphic genotypes IL10 -1082 GA and GG were more frequent in OM-prone children than in control group (RR 1.145, 95% CI 1.011-1.298; p = 0.047). However, logistic regression did not confirm IL10 -1082 polymorphic genotypes as an independent risk factor for OM proneness. The present study indicates that high-producing IL10 -1082 GA/GG genotypes may increase the risk for OM proneness in its carriers when exposed to other environmental/host risk factors (day care attendance, passive smoking, male sex, respiratory infections, and atopic manifestations). This study revealed no significant independent genetic association, but the lack of breastfeeding in infancy was found to be the only independent risk factor for development of OM-prone phenotype, implying that breastfeeding had a protective role in development of susceptibility to OM. • The pathogenesis of OM is of multifactorial nature, dependent on infection, environmental factors, and immune response of the child. • Cytokines and CD14 play an important role in the presentation and clinical course of otitis media, but a clear link with otitis media proneness was not established. What is new: • This is the first clinical and genetic study on Montenegrin children with the otitis media-prone phenotype. • The study revealed that high-producing IL10 -1082 genotypes may influence otitis media proneness in children exposed to other environmental/host risk factors.

Association of cytokine gene polymorphisms (IL‑6, IL‑12B, IL‑18) with Behcet's disease : A meta-analysis.

This study aims to investigate the association of cytokine gene polymorphisms with the risk of Behcet's disease (BD) via comprehensive meta-analysis. The Embase and PubMed databases covering the period from the earliest possible year to May2015 were searched. A total of 13eligible articles including 2,065BD patients and 1,559controls were recruited. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the associations. Potential publication bias was evaluated using Egger's linear regression test. Meta-analysis indicated associations between IL‑6 rs1800795, IL‑12B rs3212227, and IL‑18 rs1946518 in all study subjects: IL‑18 rs1946518 in the dominant model (IL‑18 rs1946518: OR= 0.48, 95 % CI:0.34-0.70, P = 0.000) and the homozygote model (IL‑18 rs1946518: OR= 0.40, 95 % CI:0.25-0.65, P = 0.000); and IL‑6 rs1800795 and IL‑12B rs3212227 in the dominant model (IL‑6 rs1800795: OR= 0.53, 95 % CI:0.39-0.72, P = 0.000; IL‑12B rs3212227: OR= 1.26, 95 % CI:1.06-1.48, P = 0.007; IL‑18 rs1946518: OR= 0.46, 95 % CI:0.33-0.65, P = 0.000). No significant evidence for associations of IL‑18 rs187238 polymorphisms with BD susceptibility was detected. In summary, this meta-analysis finds that IL‑6 rs1800795 and IL‑18 rs1946518 polymorphisms decrease the risk of BD. However, IL‑12B rs3212227 increases BD susceptibility. Further large-scale investigation of this association is necessary.

Cytokine gene polymorphisms and their association with cervical cancer: A North Indian study

IntroductionThe production of cytokines, growth factors and adhesion molecules promotes tumor progression and involves inflammation, angiogenesis and thrombosis, thus providing optimal conditions for cancer development. Materials and methodsThe present study was undertaken to evaluate association of cytokine gene polymorphisms with cervical cancer in a north Indian population. Genotyping of single nucleotide polymorphisms (SNPs) viz. IL-6-597G/A (rs1800797), IL-1β-511C/T (rs16944) and TNF-α-308G/A (rs1800629) was carried out in 100 each of cases and healthy age matched controls by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Genotype and allele frequencies were calculated by SPSS (ver.16) and gene–gene interaction was analyzed using SHEsis (ver. Online). ResultsEpidemiological studies showed that women >40years have higher risk of cervical cancer due to early pregnancies. IL-6 and TNF-α promoter polymorphisms showed significant association (P<0.001) while the SNP combinations G A T∗ and G G T∗ of IL-6-597A/G, TNF-α-308G/A and IL-1β-511C/T polymorphisms showed increased risk up to 9.0 and 3.30times respectively. ConclusionTherefore, the promoter polymorphisms in cytokine genes can be used as biomarkers to predict cervical cancer susceptibility in a north Indian population. However, such studies need to be carried out in different ethnic populations in order to discover the specific risk alleles, genotypes and combinations for disease prediction.

Association of cytokine gene polymorphisms with hepatitis C virus infection in a population from Rio de Janeiro, Brazil.

BackgroundThe host immune response is an important indicator of the outcome of hepatitis C virus (HCV) infection and disease progression. The aim of this study was to explore cytokine gene polymorphisms as a candidate for susceptibility to persistent HCV infection or HCV spontaneous clearance in a population from Rio de Janeiro, Brazil.MethodsGenetic polymorphisms in the cytokines, tumor necrosis factor-alpha (−308), transforming growth factor-beta 1 (codons 10 and 25), interleukin-10 (IL-10; −1082 and −592), IL-6 (−174), and interferon-gamma (+874) were analyzed by polymerase chain reaction sequence-specific primers in 245 patients with chronic hepatitis C (CHC), 41 spontaneous recovery (SR) patients, and 189 healthy volunteers. Further, polymorphisms in IL-28B (rs12979860, rs12980275, and rs8099917) were assessed by real-time polymerase chain reaction in all groups.ResultsThe IL-28B rs12979860 CC and rs12980275 AA genotypes were significantly associated with SR of HCV infection and response to therapy, whereas the C allele of IL-6 (−174) was associated with protection to CHC. A multivariate analysis showed that the male sex and IL-28B rs12979860 CT and TT and transforming growth factor-beta 1 (codon 10) TC genotypes were factors associated with CHC. Additionally, IL-6 (−174) C allele was increased in SR patients compared with patients with CHC.ConclusionIL-28B polymorphisms are associated with spontaneous clearance of HCV and response to therapy in a Brazilian population. Also, IL-6 (−174) C allele is involved in SR and decreased inflammation scores.

Cytokine gene polymorphisms, cytokine levels and the risk of colorectal neoplasia in a screened population of Northeast Scotland.

Cytokine gene polymorphisms modify expression and their circulating protein levels reflect inflammatory response. Chronic inflammation plays a key role in the pathogenesis of colorectal neoplasia (CRN) associated with inflammatory bowel disease, but it is not clear whether inflammation is a cause or an effect of tumours in sporadic CRN. We therefore investigated the association of cytokine gene polymorphisms and circulating cytokine levels on the risk of CRN in Northeast Scotland, which has a high incidence of CRN. We recruited two groups of patients from a screening colonoscopy cohort, either preprocedure or 3-24 months postprocedure. Participants with CRN were compared with participants with no evidence of CRN (controls). Blood-derived DNA was used to genotype polymorphisms in IL1B, IL1-RN, IL6, IL8, IL10, PTGS2 and TNFA genes. Circulating levels of high-sensitivity C-reactive protein and six cytokines [interleukin-1β (IL-1β), IL-4, IL-6, IL-8, IL-10 and tumour necrosis factor-α (TNF-α)] were measured. To examine the effect of CRN resection on marker levels, we used propensity score matching. A total of 884 patients were eligible for analysis, including 388 CRN cases and 496 controls. Cases were older (mean age 64 vs. 62 years, P<0.01) and more likely to be men (67 vs. 55%, P<0.001). Controls were more likely to be regular users of NSAID (P<0.0001). Compared with homozygous carriage of respective common alleles, proinflammatory CC genotypes of IL1B-31C>T [odds ratio (OR) (95% confidence interval (CI) 1.68 (1.03-2.73)] and PTGS2-765 C>G [OR (95% CI) 2.97 (1.05-8.46)] were each associated with an increased risk of CRN. Conversely, carriage of the A allele of IL8-251A>T was associated with a lower risk of CRN compared with the TT genotype [ORs (95% CI) 0.60 (0.41-0.86) for heterozygous, 0.88 (0.57-1.37) for homozygous, and 0.68 (0.48-0.95) for heterozygous and homozygous combined]. Compared with postprocedure cases, IL8, TNF-α and C-reactive protein levels were significantly higher in preprocedure cases, but IL4 and IL10 protein levels were significantly lower. Proinflammatory cytokine gene polymorphisms in IL1B-31 and PTGS2-765 increase the risk of developing CRN. Levels of proinflammatory IL8, TNF-α and C-reactive protein markers are significantly higher while CRN is in situ. Along with the NSAID findings, these data point to inflammation as an underlying pathogenetic mechanism in CRN.

Association of cytokine gene polymorphisms with psoriasis in cases from the Nile Delta of Egypt: Retraction.

[This retracts the article on p. 272 in vol. 56, PMID: 21772586.].

Association of cytokine gene polymorphisms with susceptibility to invasive candidiasis.

The aim of this study was to investigate the role of cytokine genes in the susceptibility to Candida infection. A total of 275 consecutive patients diagnosed with Candida infection were selected between May 2010 and May 2011, along with 305 uninfected controls. Genotyping of the IL-1β gene polymorphisms (IL1β) rs1143634, IL1βrs16944, IL8 rs4073, IL10 rs1800872, and IL10 rs1800896 was carried out using a 384-well plate format on the Sequenom MassARRAY platform. Patients with invasive Candida infections were more likely to have had an immunocompromised state, hematopoietic stem cell transplantation, solid organ transplant, solid tumor, chemotherapy within the past three months, neutropenia, surgery within the past 30 days, acute renal failure, liver failure, and/or median baseline serum creatinine. Conditional logistic regression analyses found that individuals with the rs1800896 GG genotype were associated with a higher risk of invasive Candida infections than those carrying the AA genotype (odds ratio = 0.61, 95% confidence interval = 0.37-0.94). From the results of this case-control study, we suggest that the cytokine IL-10 gene rs1800896 polymorphism might play a role in the etiology of invasive Candida infections.

Association of cytokine gene polymorphisms in peptic ulcer development in the Bashkortostan Republic

Peptic ulcer disease (PUD) is a chronic disease based on recurrent gastric or duodenal ulcers. Association analysis of common polymorphisms of the cytokines genes IL1B (rs1143634), IL1RN (rs71941886), IL8 (rs4073), IL10 (rs1800872), and TNFA (rs1800629) was conducted in 254 patients with gastric ulcer or duodenal ulcer and in 277 unrelated healthy individuals from the Bashkortostan Republic. Associations of the rs1143634C allele and the C/C genotype of the IL1B gene with PUD in ethnic Bashkirs have been revealed. The frequency of the rs4073A/A genotype of the IL8 gene was significantly higher in the control group as compared to patients infected with H. pylori. Our results confirm the significant role of rs1143634 of the IL1B gene in PUD development.