Association of tumor necrosis factor alpha, interferon gamma and interleukin 10 gene polymorphisms with peripheral neuropathy in South Indian patients with type 2 diabetes

Diabetic peripheral neuropathy (DPN) is a major global health threat and a common complication of diabetes. Peripheral nerve complications due to irregular cytokine production are eminent factors in many inflammatory diseases. The present study focused on gene polymorphisms of pro and anti-inflammatory cytokines that may be responsible for nerve damage in diabetic neuropathy. We examined three common functional SNPs primarily at the positions on genes of tumor necrosis alpha (TNFα) −308G/A, interferon gamma (IFNγ) +874A/T and interleukin (IL) 10 −1082G/A in order to establish their association with peripheral neuropathy in type 2 diabetes. Results: Genotypic frequencies obtained from TNFα −308G/A gene analysis in DPN group comprised 86.4% of G/A, 10.6% of G/G and 3% of A/A genotype, where as the control group had 94% of G/A, 2% of G/G and 4% of A/A which could not reach the statistical significance with the disease after Bonferroni correction. The IFNγ +874 A/T polymorphism in patient group revealed 33.3% of A/A, 47.5% of A/T and 19.2% of T/T genotype. The A/A genotype had attained statistical significance of P = 0.04 (P corrected); OR 2; 95% CI 1.14–3.64 when compared to controls. The IL10 −1082 G/A polymorphism in the patient group has showed 62.6% of A/A, 21.2% of G/A, 16.2% of G/G genotype, revealing significant association with G/G genotype (P < 0.01, OR 2.9; 95% CI 1.47–5.84) when compared to controls. Conclusion: Our findings indicate that the tested markers within the IFNγ and IL-10 genes, but not the TNFα gene, are significantly associated with peripheral neuropathy in South Indian type 2 diabetic patients. The study shows that the ‘high-producer’ IL-10 −1082 G/G genotype and the ‘low-producer’ IFNγ +874 A/A genotype may be responsible for the down regulation of immune response leading to inflammation in this setting.     

Single Nucleotide Polymorphisms in IL17A and IL6 Are Associated with Decreased Risk for Pulmonary Tuberculosis in Southern Brazilian Population

In Mycobacterium tuberculosis (MTB) infection, the complex interaction of host immune system and the mycobacteria is associated with levels of cytokines production that play a major role in determining the outcome of the disease. Several single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with tuberculosis (TB) outcome. The aim of this study was to evaluate the association between previously reported SNPs IL2–330 T>G (rs2069762); IL4–590 C>T (rs2243250); IL6–174 G>C (rs1800795); IL10–592 A>C (rs1800872); IL10–1082 G>A (rs1800896); IL17A -692 C>T (rs8193036); IL17A -197 G>A (rs2275913); TNF -238 G>A (rs361525); TNF -308 G>A (rs1800629) and IFNG +874 T>A (rs2430561) and pulmonary TB (PTB) susceptibility. We conducted a case-control study in individuals from Southern Brazil who were recruited between February 2012 and October 2013 in a high incidence TB city. We performed a multiplex genotyping assay in 191 patients with PTB and 175 healthy subjects. Our results suggest a decreased risk for PTB development associated with the IL17A -197A allele (OR = 0.29; p = 0.04), AA genotype (OR = 0.12; p = 0.04) and A carrier (AG/AA) (OR = 0.29; p = 0.004) and IL6 -174C carrier (CC/CG) (OR = 0.46; p = 0.04). We could not properly analyze IL17A -692 C>T (rs8193036) and IFNG +874T>A due to genotypic inconsistencies and found no evidence of association for the IL2, IL4, IL10 and TNF polymorphisms and PTB. In conclusion, our results show a protective effect of IL17 and IL6 polymorphisms on PTB outcome in Southern Brazilian population.     

Linkage and association of proinflammatory cytokines genes <Emphasis Type="Italic">IL-6, IFNG</Emphasis> and <Emphasis Type="Italic">TNF</Emphasis> with multiple sclerosis

Proinflammatory cytokines interleukin-6 (IL-6), interferon-γ (IFNg) and tumor necrosis factor (TNF) play an important role in the pathogenesis of multiple sclerosis. Based on the published data concerning the effects of the SNPs G(−308)A of TNF, A(+874)T of IFNG, and G(−174)C of IL-6 on the production of these cytokines, we investigated the relation of these polymorphisms with multiple sclerosis. Linkage and association of alleles of these genes with multiple sclerosis were analyzed by transmission disequilibrium test. In a group of 104 nuclear families of Russian ethnicity, the TNF*(−308)A allele was more frequently transmitted from healthy heterozygous parents to affected children (p = 0.01). Linkage/association of IFNG and IL-6 alleles with multiple sclerosis was not detected. Thus, the data obtained indicate that TNF is involved in susceptibility to multiple sclerosis in Russians.     

Association of IFN-gamma and IL-10 gene variants with the risk of extrapulmonary tuberculosis

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is a chronic infectious disease. Interferon-gamma (IFN-γ) is an important cytokine imparting resistance to mycobacterial diseases. It is believed that IFN-γ and Interleukin-10 (IL-10) play divergent roles in the host immune system against MTB infection. IL-10 is an important inhibitory cytokine and helps balancing the inflammatory and immune responses. IL-10 is involved in down regulation of Th1 cytokines, MHC class II antigen and co-stimulatory molecular expression on macrophages, while IFN-γ results in macrophage activation allowing them to exert the microbicidal role. The objectives were to find out the association of IL-10 (?1082 A/G) and IFN-γ (+874 A/T) single nucleotide polymorphisms (SNPs) with extrapulmonary tuberculosis in ethnic Kashmiri population. A total of 100 extrapulmonary tuberculosis cases and 102 healthy controls were analyzed for IL-10 (?1082 A/G) and IFN- γ (+874 A/T) SNPs using Allele-Specific PCR. We found a significant association of IFN-γ + 874 ‘TT’ genotype with extrapulmonary tuberculosis (p = 0.006) and in case of IL-10 (?1082 A/G) we found a significant association with extrapulmonary tuberculosis under recessive model (GG vs GA + AA) (p = 0.03) in Kashmiri population. IL-10 (?1082 A/G) and IFN-γ (+874 A/T) have a significant association with extrapulmonary tuberculosis in ethnic Kashmiri population.     

The effect of tumor necrosis factor alpha (-308G/a) and interferon gamma (+874T/a) polymorphisms on susceptibility to coronary heart disease

Abstract

Background: Coronary heart disease (CHD) is a chronic inflammatory disease, which is still regarded as a major cause of morbidity and mortality worldwide. Several studies have suggested that polymorphisms in cytokine genes are associated with the pathogenesis of CHD. The genotype distribution of Tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) genes polymorphisms have been shown to be different in various ethnic populations. This study was aimed to investigate the association of TNF-α-308?G/A and IFN-γ?+?874T/A polymorphisms with risk of CHD in an Iranian population.

Methods: A total of 187 unrelated subjects comprised 96 CHD patients and 91 healthy controls were enrolled in this cross-sectional study. The TNF-α-308?G/A and IFN-γ?+?874T/A polymorphisms were genotyped using amplification refractory mutation system-PCR (ARMS-PCR). The chi-square and logistic regression tests were used to calculate the odds ratios (ORs) as a measure of differences in genotype frequencies.

Results: A significant differences in the allelic and genotypic distribution of TNF-α-308?G/A and IFN-γ?+?874T/A polymorphisms was found between CHD patients and healthy controls (P?=?0.017, P?=?0.011, P?=?0.006 and P?=?0.002, respectively). Logistic regression analyses were also revealed statistically significant risk for CHD with respect to TNF-α-308?A and IFN-γ?+?874?T carriers either in crude or after adjustment for potential confounders (P?=?0.003 and P?=?0.006, respectively).

Conclusion: This study provides strong evidence supporting the association of TNF-α-308G/A and IFN-γ?+?874T/A polymorphisms with the increased risk of CHD. Therefore, these two cytokine polymorphisms may play a role in predisposition to coronary heart disease.     

IL10 Haplotype Associated with Tuberculin Skin Test Response but Not with Pulmonary TB

Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions −2849 , −1082 , −819 , and −592 and reconstructed the haplotypes. The IL10 low-producer haplotype −2849A/−1082A/−819C/−592C, compared to the high-producer haplotype −2849G/−1082G/−819C/−592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3–3.6) and PPD-positive controls (OR 2.09, CI 1.2–3.5). Lower IL-10 plasma levels in homozygous −2849A/−1082A/−819C/−592C carriers, compared to homozygous −2849G/−1082G/−819C/−592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy.     

Ethnic differences in cytokine gene polymorphisms: potential implications for cancer development

Differences in incidence and outcome of cancer among ethnic groups may be explained by biological and/or socio-economic factors. Genetic variations that affect chronic inflammation, a potentially important risk factor for carcinogenesis, may differ across ethnic groups. Such differences may help explain cancer disparities among these groups. Single nucleotide polymorphisms (SNPs) within cytokine genes can affect cytokine levels and the degree of inflammation. Associations between cancer and some cytokine SNPs have been suggested. However, these have not been consistently replicated among populations, suggesting that SNP function may differ according to ethnicity, or that SNPs alone do not completely account for regulation of inflammation. We examined seven polymorphisms in African-American (n = 294) and Caucasian (n = 299) newborns in Louisiana: IL1B-511C > T, IL1B-31T > C, IL1B + 3954C > T, IL1RN*2, IL10-1082G > A, IL10-592C > A, and TNF-308G > A. African-American newborns had significantly higher frequencies of IL1B-511T, IL1B-31C, IL10-1082A and IL10-592A alleles and complete linkage equilibrium between IL1B + 3954 and IL1B-31. In contrast, IL1B + 3954T, IL1RN*2, and TNF-308A were more frequent in Caucasian newborns and exhibited strong linkage disequilibrium between IL1B + 3954 and IL1B-31. All allelic frequencies were significantly different between groups. We hypothesize that these dissimilarities may contribute to differences in the inflammatory response and cancer incidence and mortality between African-Americans and Caucasians in Louisiana.     

Meta-analysis of TNF 308 G/A polymorphism and type 2 diabetes mellitus

Background and Objectives

Many investigations have focused the association between TNF 308 G/A polymorphism and risk for type 2 diabetes mellitus (T2DM). However, the sample sizes of most of the studies were small. The aim of this study is to evaluate the precise association between this variant and risk for T2DM in a large-scale meta-analysis.

Methods

All publications were searched on the association between TNF 308 G/A polymorphism and T2DM. The key words were as follows: diabetes, tumor necrosis factor and polymorphism/variant/genotype. This meta-analysis was assessed by Review manager 5.0.

Results

There were 18 studies identified. The odd ritos (ORs) and 95% confidence intervals (CI) for GA+AA versus GG genotype of TNF 308 G/A polymorphism were 1.03 (0.95–1.12), 1.03 (0.94–1.13) and 1.03 (0.78–1.36) in overall, Caucasian and Asian populations, respectively. The sensitivity analysis further strengthened the validity of this association. No publication bias or heterogeneity was observed in this study.

Conclusion

In summary, there was no significant association detected between the TNF 308 G/A polymorphism and risk for T2DM.     

IFNG polymorphisms are associated with tuberculosis in Han Chinese pediatric female population

Host genetic factors play a major role in determining differential susceptibility to human tuberculosis (TB), a re-emerging infectious disease throughout the world. Genetic variations in the IFNG gene coding for interferon gamma (IFN-γ), have been identified in TB patients. To investigate the association of the IFNG polymorphisms with TB susceptibility in Chinese pediatric population. A case–control study of 189 TB patients and 164 controls was performed using single-nucleotide polymorphism (SNP) analysis. Genomic DNA was extracted from leukocytes in peripheral blood. Three SNPs of IFNG, including ?1616C/T (rs2069705), +874A/T (rs2430561), and +3234C/T (rs2069718), were selected for genotyping and analysis. The +874A and +3234C alleles were more frequent among TB patients (P = 0.108 and P = 0.088), especially in females (both P = 0.029), although this difference was not significant since Bonferroni corrected significance threshold was 0.025 (two of three SNPs were found to be in linkage disequilibrium). More pronounced differences for the +874 and +3234 polymorphisms were found under the genotype comparison between TB cases and controls in the total population [P = 0.026 (borderline non-significance) and P = 0.020, respectively], and in the female subgroup (P = 0.020 and P = 0.020). The dominant model of inheritance was shown to be significant for +874A and +3234C alleles (both P = 0.019) in the female subgroup. The +874A and +3234C alleles were more frequently found in extrapulmonary TB patients than in controls (P = 0.039). Haplotype analysis carried out on these three SNPs showed the TTT haplotype to be more frequent in controls than in TB cases, and this difference showed a strong significance (P = 0.005). The +874A and +3234C alleles may be related to TB susceptibility in the female subgroup in the Chinese pediatric population of North China. The higher rate of +874A (known to correlate with lower IFN-γ expression) in the extrapulmonary TB subgroup suggests a sufficient IFN-γ expression to be not only an important factor for the onset of TB disease but also for limiting its dissemination to lungs.     

Association between the IFNG +874A/T gene polymorphism and leprosy resistance: A meta-analysis

Previous studies identified the variant IFNG +874A/T (rs2430561) in the first intron of the gene in association with mycobacterial infection, especially tuberculosis and leprosy. The aim of this investigation was to analyze the protective role of the T allele in relation to leprosy using a meta-analysis evaluation. Thus, 1573 patients and 1914 controls were included and analyzed in fixed effects model. The T allele is associated with a protective effect for leprosy under the dominant model (pooled OR = 0.83, 95% CI = 0.72–0.96, p = 0.011) suggesting that carriers of the IFNG +874T allele may be protected from developing leprosy. The T allele has been suggested to correlate with high interferon-γ levels. A phenotype with high IFN-γ producing and an increased inflammatory profile may account for these findings. This meta-analysis suggests that IFNG +874T allele is associated with leprosy resistance.     

Interferon gamma gene +874A/T polymorphism and intracellular interferon gamma expression in pulmonary tuberculosis

We investigated whether IFN-γ gene +874(A/T) polymorphism influences intracellular interferon gamma expression in T-cell subsets of normal healthy subjects (NHS) and pulmonary tuberculosis patients (PTB). Peripheral blood mononuclear cells were stimulated with live Mycobacterium tuberculosis (MTB) and the intracellular IFN-γ expression was studied using flow cytometry. Genotyping of IFN-γ gene +874(A/T) was done using allele specific polymerase chain reaction. Significantly increased IFN-γ expressing CD3+CD4+ and CD3+CD8+ T cells were observed in NHS with AA genotype compared to TT genotype in unstimulated (p = 0.0308 and p = 0.0157) and MTB stimulated (p = 0.0494 and p = 0.0287) cultures and this difference was not observed in PTB patients. The present study suggests that the variant genotypes of IFN-γ (+874) may be associated with altered expression of IFN-γ at the intracellular level and play an immunoregulatory role at the site of M. tuberculosis infection.     

Combinations of cytokine gene network polymorphic markers as potential predictors of myocardial infarction

With the intent to identify informative predictors of myocardial infarction (MI) development in an ethnically homogenous group of Russian men after MI (255 subjects) and in a corresponding control group (257 subjects), an analysis of genotype frequency distribution for polymorphic DNA markers (SNP) rs16944 (?511C>T, IL1B gene), rs1800796 (?572G>C, IL6 gene), rs1800872 (?592C>A, IL10 gene), rs3212227 (1159A>C, IL12B gene), rs1800629 (?308G>A, TNF), rs909253 (252A>G, LTA), rs767455 (36A>G, TNFRSF1A) was conducted. Using the Monte Carlo method and a Markov chain (APSampler), allele combinations associated both with decreased and increased MI risk were revealed. The most significant results were obtained for IL6*C/C (P = 3 × 10^?4, OR = 6.3 CI 2.37–16.75), LTA*A + IL6*G/G (FDR = 2.3 × 10^?4, OR = 0.25 CI 0.14–0.46), LTA*G/G + IL12B*A/A (FDR = 0.0053, OR = 4.92 CI 1.8–13.33), TNF*G + LTA*G/G + TNFRSF1A*A (FDR = 0.013, OR = 4.38, CI 1.6–12.01), TNFRSF1A*G + IL10*A/A + IL12B*C (FDR = 0.016, OR = 8.79, CI 2.17–35.63), TNF*G + LTA*G/G + IL10*C (FDR = 0.0105, OR = 3.54 CI 1.55–8.09).     

Interleukin-10-1082A/G polymorphism and inflammatory bowel disease susceptibility: A meta-analysis based on 17,585 subjects

A large number of studies have shown that the interleukin-10 (IL-10)-1082A/G polymorphism is implicated in susceptibility to inflammatory bowel disease (IBD). However, the results are inconsistent. We performed this meta-analysis to estimate the association between -1082A/G polymorphism in the IL-10 gene and IBD susceptibility. A total number of 18 case-control studies including 17,585 subjects were identified. No association was found between -1082A/G polymorphism and ulcerative colitis (UC) susceptibility. However, increased risk of Crohn’s disease (CD) was associated with -1082A/G polymorphism in the dominant genetic model (GG + GA vs. AA: OR = 1.22, 95% CI: 1.02–1.46, P = 0.028) and the heterozygote comparison (GA vs. AA: OR = 1.28, 95% CI: 1.05–1.55, P = 0.015). The results of this meta-analysis provide evidence for the association between IL-10-1082A/G polymorphism and susceptibility of CD. Due to several limitations in the present study, well-designed epidemiological studies with large sample size among different ethnicities should be performed in the future.     

Combination of low producer AA-genotypes in IFN-γ and IL-10 genes makes a high risk genetic variant for HIV disease progression

Rate of HIV disease progression varies considerably among individuals, host genetic makeup be one of the possible reasons. We aimed to determine association of functional single nucleotide polymorphism (SNPs), (−179G/T and +874T/A) in IFN-γ and (−1082A/G, −819C/T and −592C/A) in IL-10 genes, with the rate of disease progression or susceptibility to HIV infection. Therapy naïve HIV infected individuals from North India, categorized as slow progressors or fast progressors and HIV exposed seronegative individuals were recruited for this study. Genotyping results revealed significantly higher frequencies of low producer AA genotype at +874T/A in IFN-γ gene and −592C/A position in IL-10 gene in FPs (p < 0.002). Multifactor dimensional reduction (MDR) analysis revealed this to be a high risk combination for faster disease progression in HIV-1 infected individuals. Low producer AA genotype carriers at +874T/A in IFN-γ gene produced significantly low amounts of cellular IFN-γ. Low producing haplotype ‘ATA’ at −1082, −819 and −592 loci in IL-10 gene was significantly over-represented in FPs as compared to SPs (p < 0.01) and these individuals showed poor response to therapy in terms of CD4 count gains after one year of ART, compared to high producing haplotype (GCC) carriers. Thus, a combination of genetic variations in IFN-γ and IL-10 cytokine genes in a single host associate with HIV disease progression and may help clinicians to better manage the HIV disease if known earlier.     

Association of immune system gene polymorphisms with quantitative traits pathogenetically important for chronic virus hepatitis

The IL4 C(?590)T, IL4RA Ile50Val, and TNF G(?308)A polymorphisms were tested for association with quantitative traits important for chronic virus hepatitis, including the levels of IL4, IL10, IL12, TNF-α, fibronectin, collagenase, the proteinase inhibitor, macroglobulin, and free and protein-bound (PBO) oxyproline. Allele A of the TNF G(?308)A polymorphism was associated with a lower TNF-α production by mononuclear cells, a higher production of IL4 and IL12, and a lower PBO level. The genotype CT of the IL4 C(?590)T polymorphism was associated with a high PBO level.     

IFNG +874 T>A single nucleotide polymorphism is associated with leprosy among Brazilians

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a low virulence mycobacterium, and the outcome of disease is dependent on the host genetics for either susceptibility per se or severity. The IFNG gene codes for interferon-γ (IFN-γ), a cytokine that plays a key role in host defense against intracellular pathogens. Indeed, single nucleotide polymorphisms (SNPs) in IFNG have been evaluated in several genetic epidemiological studies, and the SNP +874T>A, the +874T allele, more specifically, has been associated with protection against infectious diseases, especially tuberculosis. Here, we evaluated the association of the IFNG locus with leprosy enrolling 2,125 Brazilian subjects. First, we conducted a case–control study with subjects recruited from the state of São Paulo, using the +874 T>A (rs2430561), +2109 A>G (rs1861494) and rs2069727 SNPs. Then, a second study including 1,370 individuals from Rio de Janeiro was conducted. Results of the case–control studies have shown a protective effect for +874T carriers (OR_adjusted = 0.75; p = 0.005 for both studies combined), which was corroborated when these studies were compared with literature data. No association was found between the SNP +874T>A and the quantitative Mitsuda response. Nevertheless, the spontaneous IFN-γ release by peripheral blood mononuclear cells was higher among +874T carriers. The results shown here along with a previously reported meta-analysis of tuberculosis studies indicate that the SNP +874T>A plays a role in resistance to mycobacterial diseases.     

A meta-analysis on the association between three promoter variants of TNF-α and Crohn’s disease

Tumor necrosis factor-alpha (TNF-α) has been regarded as a candidate gene for Crohn’s disease (CD) based on its inflammatory function in immune reaction and the clinical effectiveness of anti-TNF-α therapy. However, studies to date have reported inconsistent findings for the association between TNF-α and CD. The PubMed, EMBASE, and Medline databases were systematically reviewed from all English language publications up to April, 2011. A total of twenty-nine studies concerning the association between CD and the TNF-α promoter polymorphisms of −308G/A, −857C/T and −238G/A were identified, among of them only twenty-three studies match the inclusion criteria (including 3,843 cases and 6,260 controls) and were selected for the statistical test. We found that neither the G allele of −308G/A (OR 1.02, 95% CI 0.87–1.19, P = 0.84), C allele of −857C/T (OR 0.97, 95% CI 0.86–1.09, P = 0.57) and G allele of −238G/A (OR 0.91, 95% CI 0.70–1.18, P = 0.48), and nor their GG (OR 1.05, 95% CI 0.88–1.25, P = 0.59), CC (OR 0.98, 95% CI 0.86–1.12, P = 0.76) and GG (OR 0.92, 95% CI 0.70–1.21, P = 0.55) genotypes were associated with CD susceptibility, respectively. Our meta-analysis demonstrates that three promoter polymorphisms of TNF-α above may not confer susceptibility to CD.     

Analyses of functional IL10 and TNF-α genotypes in Behçet’s syndrome

We aim to ascertain the possible involvement of functional IL10 and TNF-α promoter polymorphisms on the susceptibility to Behçet’s syndrome (BS), to examine whether IL10 and TNF-α genotypes might work synergistically influencing susceptibility to BS. IL10 ?1082G/A, ?819C/T and ?592C/A and TNF ?308G/A polymorphisms were analyzed in 102 Turkish patients with BS and 102 healthy subjects by using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). We have found no significant associations between IL10 ?1082G/A, ?819C/T, ?592C/A, TNF-α ?308G/A polymorphisms and BS. Also, no significant correlation was found between IL10 GCC, ACC, ATA haplotypes, GCC⁺/GCC⁺, GCC⁺/GCC^?, GCC^?/GCC^? genotypes. There was no significant association between combined TNF-α/IL10 genotypes and BS. Our study indicates that functional TNF-α, IL10 genotypes or combined TNF-α, IL10 genotypes do not play a role in BS susceptibility in Turkish BS patients.     

The −1082A/G polymorphism in the Interleukin-10 gene and the risk of rheumatoid arthritis: A meta-analysis

A large number of studies have shown that the −1082A/G polymorphism (rs1800896) in the Interleukin-10 gene (IL-10) is implicated in the susceptibility to rheumatoid arthritis (RA). However, the results are inconsistent and inconclusive. The aim of this study is to analyze the association between the −1082A/G polymorphism in the IL-10 gene and the RA risk by meta-analysis. A total of 1480 cases and 1413 controls in 10 case–control studies were included in this meta-analysis. The results indicated that the G allele carriers (GG + GA) had a 25% decreased risk of RA, when compared with the homozygote AA (odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.59–0.93). In the analysis in Europeans, significant decreased risks were associated with the G allele carriers (OR = 0.73 and 95% CI: 0.57–0.93 for GG + GA vs. AA). The results from this meta-analysis provide evidence for the association between the IL-10 −1082A/G polymorphism and the risk of RA. To further evaluate gene × gene and gene × environment interactions between the polymorphisms in the IL-10 gene and RA risk, more studies with large groups of patients are required.     

Cytokine gene polymorphism and asthma susceptibility, progress and control level

Asthma is a multifactor inflammatory disorder, and its management requires understanding of its various pathogenesis and control mechanisms. Cytokines and other inflammatory mediators are important factors in asthma pathophysiology. In this study, we evaluated the role of cytokine polymorphisms in the asthma susceptibility, progress, control, and lung functions. IL-4-C590T polymorphism by PCR-RFLP method, IFN-γ T+874A, TNF-α-A308G, IL-6 G−174C and TGF-β T+869C variants by ARMS-PCR method and IgE serum level by ELISA technique were determined in 81 asthmatic patients and 124 normal subjects. Asthma diagnosis, treatment and control levels were considered using standard schemes and criteria. TNF-α−308GA genotype was more frequent in asthmatics (P = 0.025, OR 3.352), and polymorphisms between different asthma control levels (P > 0.05) were not different. IFN-γ+874AT genotype had a positive correlation with the familial history of asthma (P = 0.034, OR 2.688). IL-6−174C allele (P = 0.045), TNF-α−308GG genotype (P = 0.002) and TNF-α−308G allele (P = 0.004) showed reduced values, and TNF-α−308GA genotype (P = 0.002) increased FEF25-75 value in asthmatics. IFN-γ+874AA genotype caused a decrease in FVC factor (P = 0.045). This study showed that TNF-α−308GA is a risk factor for asthma, but cytokine gene variants do not affect asthma control and IgE serum levels. Variants producing lower levels of IL-6, TNF-α and IFN-γ are associated with reduced pulmonary capacities. To achieve an appropriate schema for asthma management, further studies with consideration of different aspects in a larger group of patients would be more elucidative.