Association Of Cytokine Gene Polymorphisms Research Articles

Association of Cytokine Gene Polymorphisms with Gastritis in a Kazakh Population

Gastritis and gastric cancer are the most common diseases in the Kazakh population. Polymorphisms in genes coding of cytokines have been played important role with gastric disease risk. The risk alleles of cytokines in patients with gastritis can predict the risk of developing gastric cancer. The aim of this study was to investigate cytokine gene polymorphisms as risk factors for the development of gastritis in a case-control study with gastritis patients and healthy individuals from the Kazakh ethnic group, living in North Kazakhstan. The polymerase chain reaction followed by direct sequencing were used for detection of two functional polymorphisms in the IL1 gene family, and TaqMan SNP Genotyping Assay Sets were applied for three potentially functional polymorphisms in the IL10 gene, and one in the TNFA promoter. Association analysis of studied allelic variants and the development of gastritis in H. pylori- positive patients showed that IL1B -31C/C, IL1B -511T/T and IL1RN -2/2 allelic variants were associated with development of gastritis (OR=1.8 (1.07-3.16), p=0.025; OR=1.7 (1.04-2.99), p=0.035, and OR=4.92 (2.45-9.85), p<0.001) respectively. Haplotype C-T that combines both homozygous allelic variants of IL1B gene also had a statistically significant association with slightly higher OR (OR: 1.43, 95% CI: 1.08-1.88). The data from the current study showed that the genotype IL-1B -511T/-31C-IL1-RN-2 and H. pylori infection increase risk of gastritis in the Kazakh population. That genotype combination might be a factor increasing the risk of developing gastric cancer.

Association of Cytokine Gene Polymorphisms in Patients with Tuberculosis and Their Household Contacts

Cytokine gene polymorphisms are known to be associated with functional differences in cytokine regulation and may affect host susceptibility to tuberculosis (TB). Contacts are important group in developing tuberculosis infection and are 10-60 times more likely to develop TB than general population. The present study was carried out in patients with TB (N=176), their household contacts (HHC; N=155) from Free Chest TB Clinic PPM DOTS (1TU) covering 500,000 population at Mahavir Hospital and Research Centre, Hyderabad, and healthy controls (HC; N=170) also included. The association of single-nucleotide polymorphisms (SNPs) in the promoter region of TNF-α (-308G/A), IL-2 (-330T/G), IL-4 (-589C/T) and in exon region of TGF-β1 (+869T/C) genes was assessed by ARMS & PCR-RFLP using specific primers in the above-mentioned subjects. The differences in allelic or genotypic frequencies of TNF-α (-308G/A) between patients, their HHC and HC were not statistically significant (P>0.05). IL-2 (-330T/G) TG genotype was significantly different between patients, HHC compared to HC (P<0.002, OR-1.997, 95%CI-1.260-3.168, P<0.03, OR-1.602, 955CI-1.003-2.561).IL-4 (-589C/T) CC genotype was significantly different between patients and HC (P<0.03, OR-1.791, 95%CI-1.009-3.189) as well as between HHC and HC at P<0.0001, OR-2.56, 95%CI-1.448-4.545. In addition, the TGF-β 1 (+869T/C) TC genotype was significantly associated with susceptibility to tuberculosis in patients when compared against HC(P<0.0001, OR-3.416, 95%CI-2.063-5.670) and HHC (P<0.0001, OR-2.357, 95%CI-1.439-3.868), respectively.MDR analysis indicated that TT genotype of TGF-β1 with TT and CT genotypes of IL-4 showed high risk with GA, TT genotypes of TNF-α, IL-2, respectively. Our results suggest that IL-2 (-330T/G), IL-4 (-589 C/T) and TGF-β1 (+869T/C) gene polymorphisms may be associated with TB susceptibility.

Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus.

Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.

Cytokine gene polymorphisms in acute cellular rejection following living donor liver transplantation: analysis of 155 donor-recipient pairs.

Despite improvements in immunosuppressive therapy, acute cellular rejection (ACR) remains an important cause of graft loss in patients undergoing liver transplantation. Recently, associations between cytokine gene polymorphisms in recipients and the occurrence of ACR have been reported. However, most studies did not investigate gene polymorphisms in donors or were limited by the number of cases investigated. We examined 155 living donor liver transplantation (LDLT) patients treated at Nagoya University or Kyoto University from 2004 to 2009. The following gene polymorphisms in recipients and donors were analyzed: tumor necrosis factor A (TNF-A) T-1031C, interleukin 2 (IL-2) T-330G, IL-10C-819T, IL-13C-1111T, and transforming growth factor B (TGF-B) T29C. Forty-seven recipients (30.3%) developed early ACR. Of the investigated gene polymorphisms, the IL-13 -1111C/C genotype in recipients was significantly associated with a higher incidence of ACR relative to the other two genotypes (OR=2.64, 95% CI 1.19-5.86, p=0.017), while we showed the lack of association between investigated gene polymorphisms in donors and ACR incidence. The IL-13 -1111C/C genotype in recipients might be a risk factor for ACR in LDLT, and this might contribute to individualized immunosuppression strategies for recipients. On the other hand, the current study showed no associations of cytokine gene polymorphisms in donors with ACR incidence.

Molecular genetic analysis of polymorphisms pertaining to the susceptibility to chronic asthma in Egyptian patients

BackgroundAsthma is a multifactorial inflammatory disorder that might result from the interaction of multiple genes and environmental factors. Several studies of genetic epidemiology have reported the association of cytokine genes with asthma among various populations. However, the results are inconsistent and inconclusive. ObjectiveTo determine the association of cytokine gene polymorphisms with asthma susceptibility in adult Egyptian cases. SubjectsThe study included, 50 adult Egyptian asthmatic cases with a mean age of 53.62±14.61years in addition to 98 healthy individuals as control. For all participants, DNA was isolated from peripheral blood samples and analyzed for TNF-α-308 G>A, IL-10-1082 G>A, IL-6-174 G>C and IL-1Ra VNTR polymorphisms. ResultsThe comparison between the cases and controls has showed significantly higher frequency of the genotypic polymorphisms: IL-10-1082 AG+GG (dominant mode) (76.1% vs. 91.8%, p=0.01, OR=0.3, 95% CI (0.1–0.7), TNF-α-308 GA+AA (dominant mode) (72.0% vs. 93.9%, p=0.001, OR=0.17, 95% CI=0.06–0.47) and IL-1RA VNTR heterozygous genotype A1A2 (90.0% vs. 58.8%, p=0.0003). Otherwise, compared to controls, cases showed statistically non-significant frequency of genotypes corresponding to IL-6-174 CC+GC vs. GG (dominant mode) (92.0% vs. 94.9%, p=0.5, OR=0.6). ConclusionsThe IL-10, TNF-α and IL-1Ra allelic variants showed a potent association with chronic asthma among Egyptian cases that might be used as markers with a potential impact on prophylactic and or therapeutic measures for asthma control. Whereas the IL-6-174 allelic variants showed no association with chronic asthma among Egyptian cases.

Association of Cytokine Gene Polymorphisms with Oral Lichen Planus in Malayalam-Speaking Ethnicity from South India (Kerala)

Oral lichen planus (OLP) is a chronic mucocutaneous condition that affects the oral mucous membrane as well as skin. It is a chronic cell-mediated autoimmune condition where the T-cell-mediated immune response plays an important part in the pathogenesis by causing damage to basal keratinocytes in oral mucosa. Cytokine gene polymorphisms have an unquestionable role in the orchestration of the immune response, leading to different functional scenarios, which in turn influence the outcome of the disease establishment and evolution. The purpose of this study was to understand the role of these cytokine gene polymorphisms in the tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 genes with OLP in 101 individuals of Malayalam-speaking ethnicity from South India (Kerala). We further investigated the role of these polymorphisms in patients suffering from OLP with other comorbid factors. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism. The results demonstrate that the A allele in the TNF-α -308 polymorphism could play an important role in the susceptibility to OLP. IL-1β +3954 in OLP was associated with other comorbid factors in both allelic and genotypic combinations. However, when patients suffering from OLP were stratified to understand the involvement of other comorbid factors, we observed that the T and C alleles were independent risk factors for chronic periodontitits and diabetes mellitus. On the other hand, IL-6 -597 did not show any disease association with OLP in the study population. This study indicates that proinflammatory cytokines are an important factor in understanding the disease burden of OLP and their comorbid factors.

Association of cytokine gene polymorphisms and serum concentrations with the outcome of chronic hepatitis B

ObjectiveThe present paper investigated possible correlations between the clinical presentation of hepatitis B and the TNF-α −308G/A, IFN-γ +874A/T, TGF-beta1 −509C/T, and IL-10 −1081A/G polymorphisms and associated serum levels of these cytokines. MethodsFifty-three hepatitis patients were selected and divided into two groups: A – inactive (n=30) and B – chronic hepatitis/cirrhosis (n=23). The control group consisted of 100 subjects who were positive for anti-HBc and anti-HBs. The serum concentrations of the cytokines were determined by immunoenzymatic assays. The polymorphisms of the cytokines genes were assessed by PCR and PCR-SSP. ResultsThe mean serum levels of IFN-γ of the control group were significantly higher than those of groups A and B, whereas the mean levels TGF-beta1 were significantly higher in groups A and B in comparison with the control. In the case of IL-10, the mean serum level recorded in the control group was significantly higher than that of group B. The TNF-α −308AG genotype was considerably more frequent in group B (43.3%) than the control (14.4%). ConclusionHigher serum levels of IFN-γ and TGF-beta1 were associated with chronic hepatitis B, and lower serum levels of IL-10 were found in patients with the active disease. Furthermore the presence of allele A of the TNF-α −308 polymorphism suggest a risk of the progressive disease.

Lack of association between genetic polymorphisms in cytokine genes and tumor recurrence in patients with hepatocellular carcinoma undergoing transplantation

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains one of the most common causes of poor long-term survival. However, the host genetic factors affecting increased risk of tumor recurrence after transplantation have not been thoroughly elucidated. The present study was designed to investigate the association of cytokine gene polymorphisms with the risk of tumor recurrence in LT patients for HCC. Eleven single-nucleotide polymorphisms within the promoter regions of 7 cytokine genes, i.e., the IL-1 family (IL-1alpha and IL-1beta), IL-6, IL-8, IL-10, TNF-alpha, and TGF-beta1, were genotyped in 93 HCC patients treated with LT using DNA sequencing. The association between these polymorphisms and the risk of tumor recurrence was evaluated while controlling confounding clinical variables. The genotype frequency of IL-10 -1082 A/G in patients with and without recurrence of HCC was AA 83.3%, GA 16.7% and AA 97.6%, GA 2.4%, respectively. The association between IL-10 -1082 GA and recurrence was significant (P=0.033). No other single-nucleotide polymorphism in the cytokine gene was found to be associated with recurrence. Kaplan-Meier survival curves showed that the homozygous AA patients had a significantly longer mean recurrence-free survival than heterozygous GA patients (23.5 vs 5.7 months, P=0.001). However, multivariate analysis failed to reveal that the GA genotype of IL-10 -1082 A/G was an independent indicator of recurrence. This study suggests the lack of association of selected cytokine gene polymorphisms with HCC recurrence after LT in the Han Chinese population. The finding does not exclude the idea that other cytokine polymorphisms could act as candidate biomarkers of disease prognosis.

Cytokine Gene Polymorphisms and Severe Acute Graft-Versus-Host Disease (grade ≥II) After Allogeneic Hematopoietic Stem Cell Transplantation From HLA Identical Siblings

AbstractAbstract 4180Graft-versus-host disease (GvHD) is one of the most important complications after allogeneic hematopoietic stem cell transplantation (HSCT) and influences morbidity and mortality, even when the donor is a human leucocyte antigen (HLA)-matched sibling. Polymorphisms at genes coding for several proinflammatorycytokines and for their related receptors or receptor inhibitors are involved in this complication.To assess the role of cytokine gene polymorphisms on acute GvHD (aGVHD), we analysed 189 pairs of donor and recipients transplanted from HLA identical sibling for malignant hematological diseases between 2000 and 2007, using a non T depleted graft after a myeloablativeor a reduced intensity conditioning regimen. Material and methods:The median age of the recipients at transplantation was 43.4 years (1–68). Two third of the patients received bone marrow before myelo-ablative conditioning regimen and the median delay between diagnosis and transplantation was 9 months (1–76).Five different polymorphisms from 3 cytokine genes were analyzed: IL-10 –592C/A, -819C/T and -1082G/A, IL-1b -511A/G and TGFb1 –509C/T.All the pairs were studied for each gene polymorphism using the Taqman technology as previously described (Malkki2007). Each kit contains several primers pairs for amplification and two allele-specific probes, each of them conjugated with a different fluorescent marker. After amplification, analysis was driven on a Roche LC480 platform. The interpretation of the final results was performed using allelic discrimination specific software.In our study, the frequencies of the TGFb1, IL1b, and IL-10 genotypes in recipients and donors were almost equal, and were consistent with previously reported results for the Caucasoid population and with the NCBI SNP databases. Results:Univariate analysis found a significant negative impact of donor genotypes carrying IL1b A allele (p=0,02) or IL10–592 A allele (p=0,03) on aGvHD.We did not find any effect associated with IL10–819 and -1082 polymorphisms, but as previously described (Lin 2003), the presence of IL10 A-T-A haplotype in the donor, significantly increased the risk of aGVHD (p=0.043). We performed a multivariate analysis on aGVHD incidence taking into account TGFb1–509, IL-10–592 and IL1bpolymorphisms, together with other known risk factors.A higher incidence of aGVHD was found in pairs where donor has an IL1b A allele (HR 4,16 - p=0,0031) and increased when the donor is A/A (HR>15 – p=0,0091). For IL10–592, the impact of the A allele was found different when carried by the donor (higher risk of aGVHD, HR 3,52 – p=0,00083) or the recipient (lower risk of aGVHD, HR 0,48 – p=0,024), but this effect seems only significant in pairs where donor did not carry any A allele (rec AC × don CC – HR 0.2 – p=0.05). Donor with TGFb1–509 T allele was found to have a significant lower risk of aGVHD (HR 0,42 – p=0,02). (table 1).The role of the cytokine cascade in the physiopathology of GVHD is well established. Our study documents the possible role of IL-1b, TGFb1and IL10 gene polymorphisms in this setting.A proven association of cytokine gene polymorphisms with acute GVHD would enable the clinician to modify the therapeutic strategy and enhance the outcomes.Table 1CytokineAllele recHRpAllele donHRpRecx donReferenceHRpIL1bA2.130.036AG × AGGG × GG4.160.0031GG × AGGG × GG4.350.028AA × AAGG × GG>150.0091TGFbT0.420.02CC × CTCC × CC0.250.012CT × CTCC × CC0.140.0013IL10-592A0.480.024A3.520.00083AC × ACCC × CC2.460.038CC × ACCC × CC4.930.013ACx CCCC × CC0.20.05 Disclosures:Nicolini:Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Association of Cytokine Gene Polymorphisms in Patients with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a major health problem. The disease is driven by abnormal inflammatory reactions in response to inhaled particles and fumes. Therefore, inflammatory mediators are postulated to be of distinct importance. Keeping in view of the above facts; we investigate the role of polymorphisms of cytokine genes in the genetic predisposition of COPD. In this present case-control study, the allele and genotype distributions of IL1B, IL1RN, TNF-α, and IL4 were studied in COPD patients (N=204) and healthy individuals (N=208). Genomic DNA was obtained by whole blood and genotyping was carried out by a polymerase chain reaction (PCR) based Restriction Fragment Length Polymorphism technique. Genotype IL1RN*2/IL1RN*2 was identified as protective for male COPD, its frequency being 8.7% in COPD patients and 14.6% in healthy subjects (p=0.017; OR=0.53), but IL1RN*1/IL1RN*2 turned out to be a risk factor for females COPD. No significant differences were found between the groups of COPD patients and healthy subjects concerning the genotype frequencies of the polymorphisms T (-511) C of IL1B and 70bp VNTR of IL-4. Genotype GA of the TNF-α polymorphism G (-308) A was more common in the COPD patients than in the controls (20.5% vs.14.4%; p=0.107), and allele A was significantly associated with COPD patients (p=0.023; OR=0.65). IL-1RN *2 allele appears to be significantly associated with the COPD female patients and TNF-α-308A allele is a risk factor for the development of COPD.

Association of cytokine gene polymorphisms with long-term humoral response in children vaccinated against hepatitis B in infancy

Objective To investigate the relationship between cytokine gene polymorphisms and long-term humoral response in children vaccinated against hepatitis B during infancy.Methods A total of 293 children (6.08±0.59 years old) who received three doses of hepatitis B vaccine according to a 0-,1-,6-month schedule during infancy and were negative for HBsAg and/or anti-HBc,were enrolled.Of them,83children with anti-HBs ＜10 mIU/ml were considered as long-term poor responders ( group A),and 210 others with anti-HBs ≥ 10 mIU/ml were defined as long-term responders ( group B).A total of 11 single nucleotide polymorphisms (SNPs) of IL-1β,IL-2,IL-4,IL-10,IL-12B,and IL-13 were detected with PCR-restriction fragment length polymorphism.Results The allele frequencies of -33T,-589T,and 2979T in IL-4 gene in group A were 86.1%,86.1% and 90.4%,respectively,higher than those in group B (76.0%,76.9%,and 83.3%,respectively,all P＜0.05).In IL-4 gene,frequencies of TT genotype at position -33 and -589 in group A were 74.7% and 75.9% respectively,higher than those in group B (57.1% and 59.0% respectively,both P＜0.01 ),while the frequencies of CT at position -33 and -589 in group A was 22.9% and 20.5% respectively,lower than those in group B (37.6% and 35.7% respectively,both P＜0.05).The genotype distributions of IL-4 2979 and the allele or genotype distributions of 8 other SNPs showed no significant differences between group A and group B.Conclusion Polymorphisms at position -33,-589,and 2979 in IL-4 gene are associated with the long-term humoral response in children vaccinated against hepatitis B during infancy. Key words: Cytokine; Gene polymorphisms; Hepatitis B vaccine; Anti-HBs

A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis

We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case-control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) -1722T/C, CTLA-4 -318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36-0.54; TT vs. TG + GG: OR 0.48, 95% CI 0.39-0.59; TT + TG vs. GG: OR 0.74, 95% CI 0.66-0.83; T vs. G: OR 0.72, 95% CI 0.66-0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.

Associations of cytokine gene polymorphisms with post-stroke depression

Objectives. Inflammatory cytokines are implicated in the pathophysiology of both stroke and depression, and their production is influenced by the transcriptional activity of particular gene polymorphisms. We hypothesised that alleles related to higher pro-inflammatory and/or lower anti-inflammatory cytokine production would be associated with post-stroke depression (PSD). Methods. In 276 stroke cases, depression was diagnosed using DSM-IV, and classified into major PSD (N = 29), all (major plus minor) PSD (N = 77), and control (N = 199) groups. Genotyping for six pro-inflammatory polymorphisms (TNF-α –850C/T and –308G/A, IL-1β –511C/T and + 3953C/T, IL-6 –174G/C, and IL-8 –251T/A) and two anti-inflammatory polymorphisms (IL-4 + 33T/C and IL-10 –1082G/A) was conducted. Individual associations with PSD were estimated using logistic regression models. Total numbers of potential risk alleles were calculated for pro-inflammatory and anti-inflammatory cytokine genes and analysed against depression using χ2-tests. Results. The IL-4 + 33C/C genotype was associated with major PSD, and the IL-10 –1082A/A genotype was associated with all PSD. Increasing numbers of risk alleles for these two anti-inflammatory cytokine genotypes were significantly associated with both PSD categories. No significant associations were found with any pro-inflammatory cytokine allele. Conclusions. Alleles associated with reduced anti-inflammatory cytokine function were associated with PSD, supporting the cytokine hypothesis in its etiology.

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

Background:Psoriasis is a chronic inflammatory skin disease with an immunogenetic background. This work was planned to check for the association of polymorphisms related to cytokine genes TNF-α-308 (G/A), IL-10-1082 (G/A), IL-6-174 (G/C), and IL-1Ra (VNTR) with psoriasis in cases from Egypt.Materials and Methods:This work included 46 cases with psoriasis recruited from the Dermatology Departments, University Hospitals, Nile Delta region of Egypt. They included 14 males and 32 females with an age mean ± SD of 46.68 ± 12.16 years and range of 15–70 years. Their genotypes were compared to 98 healthy controls of matched age and sex from the same locality. Genotyping was done through deoxyribonucleic acid amplification using PCR with sequence specific primers for polymorphic alleles.Results:Compared to controls, cases showed significant higher frequency of certain genotypes including IL-6-174 CC (P < 0.001, OR = 6.7), IL-10-1082 GG (P < 0.05, OR = 5.1), and TNF-α-308 GG (P < 0.05, OR = 3.7). TNF-α-308 GG and IL-10-1082 GG genotypes were higher among cases with plaque subtype of moderate severity. Combined heterozygosity for IL-10 GA, IL-6 GC with TNF GA showed a significant low frequency among studied cases.Conclusion:Genetic polymorphisms related to IL6, IL10, and TNF-α genes showed a particular pattern of association with psoriasis that may have a potential impact on disease counseling and management.

Association of cytokine gene polymorphisms with chronic obstructive pulmonary disease in Macedonians.

The aim of this study was to examine the association of 22 cytokine gene polymorphism in Macedonians with chronic obstructive pulmonary disease (COPD). The sample of the population comprised of 301 normal respondents and 62 patients with COPD. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific priming (PCR-SSP). Positive (susceptible) association was found between patient with COPD and IL-1alpha -889/C allele; where as negative (protective) association among was found for the following alleles IL-1beta +3962/C; IL-12B -1188/A; IFNgamma +874/T; IL-2 -330/G; IL-4 -1098/G and IL-4-33/C. We found positive (susceptible) association between patients with COPD and following genotypes: IL4 -33/T:T; IFNgamma +874/A:A; IL-4 -1098/T:T ; IL-1alpha -889/C:C; IL-1beta +3962/C:T; IL-12B -1188/C:C; IL-4Ralpha +1902/G:G; IL-10 -1082/G:G; IL-2 -330/T:T; IL-4 -590/C:C; and IL-1alpha -889/C:T. Negative (protective) association between patients with COPD and following genotypes was found: IFNgamma +874/A:T; IL-4 -33/C:T; IL-4 -1098/G:T; IL-2 -330/G:T; IL-1beta +3962/C:T; IL-4 -590/C:T; IL-10 -1082/A:G; and IL-4 -33/C:C. Positive (susceptible) association between patients with COPD and following haplotypes was found: IL-4/TCT; IL-10/ATC; and IL-2/TG, and negative (protective) association was found between the patients with COPD and haplotypes for: IL-4/TTC; and IL-4/GCC. It could be concluded that several cytokine polymorphisms are positively (susceptible), or negatively (protective) associated with COPD in Macedonians.

Single Nucleotide Polymorphisms of Cytokine Genes are Associated with Fibrosis of the Intrahepatic Bile Duct Wall in Human Clonorchiasis

This study examined the association of cytokine gene polymorphisms with intrahepatic bile duct wall fibrosis in human clonorchiasis. A total of 240 residents in Heilongjiang, China underwent ultrasonography, blood sampling, and stool examination. Single nucleotide polymorphism (SNP) sites for IFN-gamma (+874 T/A), IL-10 (-1,082 G/A, -819 C/T, -592 C/A), TNF-alpha (-308 G/A), and TGF-beta1 (codon 10 T/C, codon 25 G/C) genes were observed with the TaqMan allelic discrimination assay. No significant correlation was observed between individual cytokine gene polymorphisms and intrahepatic duct dilatation (IHDD). Among individuals with clonorchiasis of moderate intensity, the incidence of IHDD was high in those with IFN-gamma intermediate-producing genotype, +874AT (80.0%, P = 0.177), and in those with TNF-alpha low-producing genotype, -308GG (63.0%, P = 0.148). According to the combination of IFN-gamma and TNF-alpha genotypes, the risks for IHDD could be stratified into high (intermediate-producing IFN-gamma and low producing TNF-alpha), moderate, and low (low-producing IFN-gamma and high producing TNF-alpha) risk groups. The incidence of IHDD was significantly different among these groups (P = 0.022): 88.9% (odds ratio, OR = 24.0) in high, 56.5% (OR = 3.9) in moderate, and 25.0% (OR = 1) in low risk groups. SNP of IFN-gamma and TNF-alpha genes may contribute to the modulation of fibrosis in the intrahepatic bile duct wall in clonorchiasis patients.

Association of cytokine gene polymorphisms in CWP and its severity in Turkish coal workers

Cytokines appear to play a key role in some inflammatory reactions affecting the interactions among pro- and anti-inflammatory mechanisms that result in several diseases such as coal workers' pneumoconiosis (CWP). In this study, to determine the cytokine gene profiles of Turkish coal miners, we performed genotyping analysis to investigate the polymorphisms of CWP-related pro-inflammatory (TNFA, IL1A, IL1B, and IL6) and anti-inflammatory cytokines (IL-1RN and TGFB1). An additional goal was to observe whether these cytokine gene polymorphisms influence the development risk and severity of. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TNFA (-238) gene polymorphism principally affected CWP development and severity (OR = 3.47: 95% CI, 1.12-10.77 and OR = 4.30: 95% CI, 1.25-14.74, respectively) and also risk of CWP (OR = 3.79: 95% CI, 1.37-10.46). The TNFA (-308) variant was associated with a risk for the CWP severity (OR = 2.84: 95% CI, 1.08-7.39). A protective effect of IL6 was found on the development (OR = 0.48: 95% CI, 0.21-0.93) and severity of CWP (OR = 0.37: 95% CI, 0.15-0.91). We suggest that TNFA (-238) variant may be a risk factor in both development and the severity of CWP, while TNFA (-308) variant seems to be important only in disease severity. On the other hand, IL6 variant may have a protective effect on the development and disease severity.

Association of cytokine gene polymorphisms with bronchial asthma in Macedonians.

Bronchial asthma is a multifactorial disease whereby both environmental and genetic factors contribute to its aetiology and/or clinical severity. The aim of this study was to examine the association of 22 cytokine gene polymorphism in the Macedonian population with bronchial asthma (BA). The sample of the population comprised of 301 normal unrelated individuals and 74 patients with BA. Cytokine genotyping was performed by PCR. Susceptible cytokine polymorphisms for BA for ten genotypes (IL-4 -1098/T:T, TNF-alpha -238/A:G, IL-4 -590/C:C, IL-2 +166/T:T, IL-2 -330/T:T, IL-10 -1082/G:G, IFNgamma utr5644/T:T, IL-10 -1082/A:A, IL-1beta +3962/T:T, IL-6 -174/G:G), six diplotypes, four haplotypes, and two alleles were found. Protective cytokine polymorphisms for BA for seven cytokine genotypes (IL-4 -1098/G:T, TNF- alpha -238/G:G, IL-2 -330/G:T, IL-4 -590/C:T, IFNgamma utr5644/A:T, IL-1beta +3962/C:T, IL-10 -1082/A:G), six cytokine diplotypes, four cytokine haplotypes, and four cytokine alleles were found. We concluded that several cytokine polymorphisms are protective, or susceptible associated with BA in population of Macedonians.

Cytokine gene polymorphisms in periodontal disease: a meta‐analysis of 53 studies including 4178 cases and 4590 controls

We conducted a systematic review and a meta-analysis, in order to investigate the potential association of cytokine gene polymorphisms with either aggressive or chronic periodontal disease. A comprehensive literature search was performed. We retrieved a total of 53 studies summarizing information about 4178 cases and 4590 controls. Six polymorphisms were included in our meta-analysis which are the following: IL-1A G[4845]T, IL-1A C[-889]T, IL-1B C[3953/4]T, IL-1B T[-511]C, IL-6 G[-174]C and TNFA G[-308]A. Random effect methods were used for the analysis. We calculated the specific odds ratios along with their 95% confidence intervals to compare the distribution of alleles and genotypes between cases and controls. Using random effect methods we found statistically significant association of IL-1A C[-889]T and IL-1B C[3953/4]T polymorphisms with chronic periodontal disease without any evidence of publication bias or significant statistical heterogeneity. A weak positive association was also found concerning IL-1B T[-511]C and chronic periodontal disease. No association was found for all the cytokines examined as far as the aggressive form of the disease is concerned. Future studies may contribute to the investigation of the potential multigenetic predisposition of the disease and reinforce our findings.

Association of Cytokine Gene Polymorphisms With Rate of Decline in Lung Function

To investigate whether genetic variants involved in cytokine expression are associated with the age-related rate of decline in forced expiratory volume in 1 second (FEV1). Functional polymorphisms in the TNFalpha, TGF beta 1, IL-1 beta, IL-1RN, IL-13, and IL-8 genes were investigated in 374 active firefighters with at least five pulmonary function tests. A protective effect was found between the presence of the TGF beta 1 -509 TT genotype and rate of decline in FEV1 (P = 0.043). Carrying an A allele at TNFalpha -308 (P = 0.010) and GG genotype at TNFalpha -238 (P = 0.028) was associated with a more rapid rate of FEV1 decline. The TNFalpha -308A/-238G haplotype was also associated with an increased rate of decline as compared with the other haplotypes. Interindividual variability in progressive decline in FEV1 may be explained in part by genetic variations within genes involved in inflammatory responses.