Cytokine Gene Polymorphisms In Patients Research Articles

Cytokine Gene Polymorphisms in Patients with Chronic Inflammatory Demyelinating Polyneuropathy.

Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 (rs1800896, rs1800871, rs1800872 and rs3024505), IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients (p = 0.049), but the GA genotype prevailed among the patients (p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs (p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 (p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients (p = 0.049) and the CG heterozygote in the HCs (p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier (p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations.

Analysis of cytokine gene polymorphisms in patients with chronic diffusional liver diseases in Perm krai

Aim. To estimate the concentration of tumor necrosis factor-alpha (TNF-α), interleukin-6 (interleukin, IL-6), vascular endothelial growth factor (VEGF) in blood serum and to analyze the polymorphism of TNF-α cytokine genes in region 308G / A (rs1800629), IL-6 in region 174G / C (rs1800795) and VEGFA in region 634G / C (rs2010963) in patients with chronic diffuse liver diseases (CDLD) living in the Perm region. Materials and methods. In 193 patients with CDLD and 90 healthy donors, the concentration of cytokines in the blood serum was studied by ELISA and the analysis of cytokine gene polymorphism by PCR was performed. Results. In patients with CDLD, the concentration of pro-inflammatory cytokines TNF-α, IL-6 and the level of VEGF in the blood serum were significantly higher than in the control (p <0.001, respectively), while the maximum level of inflammation markers was noted in liver cirrhosis, and VEGF production - in chronic hepatitis C. Comparative analysis of single nucleotide polymorphisms of cytokine genes showed significant differences in the occurrence of the GA and AA genotypes of the TNF-α gene (G-308A), the carriage of the CG variant of the IL-6 gene (C-174G), as well as the C allele and CC homozygote for marker VEGF (G-634C), which in the population of patients with CDLD in the Perm region were recorded significantly more often than in the cohort of donors, which allows us to consider them as genetic markers of the risk of developing CDLD. Conclusion. An increase in the concentration of pathogenetically significant cytokines TNF-α, IL-6 and VEGF in liver diseases can develop against the background of gene polymorphisms of these molecules. Genetic markers can be used to assess the risk of developing and progression of CDLD.

TNF-α and IL-1 β Cytokine Gene Polymorphism in Patients with Nasal Polyposis.

Nasal Polyp (NP) is a benign mass of the paranasal sinuses that protrudes into the nasal cavity. The exact underlying pathogenesis is not known. In this study we aimed to determine the genetic susceptibility of NP formation in relation to TNF-α-308 and IL-1β-511 promoter region gene polymorphisms. A total of 71 patients with NP with asthma (n=21) or without asthma (n=50) were taken as the study group, and 91 healthy volunteers were taken as the control group. Blood was gathered into EDTA-containing tubes, and patient DNA was extracted. The polymorphisms of the IL-β and TNF-α cytokine genes were analyzed using real time polymerase chain reaction. The GG genotype in the TNF-α-308 region and the CC genotype in the IL-1β-511 region were found to be risk factors for NP formation (OR: 9.2, p=0.007 and OR: 33.3, p=0.001, respectively). Regarding allelic frequencies, the G allele at the TNF-α-308 promoter region was a risk factor for NP formation (OR: 6.06, p<0.001). TNF-α GG genotype in the -308 promoter region and the IL-1β CC genotype in the -511 region are genetic risk factors for NP formation.

Investigation of cytokine gene polymorphisms in patients with psoriasis vulgaris

Investigation of cytokine gene polymorphisms in patients with psoriasis vulgaris

Cytokine gene polymorphisms in patients with age-related macular degeneration

To establish possible association between age-related macular degeneration (AMD) and cytokine genotype polymorphisms; for that promoter regions of a number of cytokine genes were studied, namely, TNF-A863C, TNF-A308G, TNF-A238G, IL1β-C-31T, IL4-C590T, IL6-C174G, and IL10A-1082G. A total of 102 AMD and 100 non-AMD participants in the same age range were examined at the Novosibirsk branch of the Academician S.N. Fyodorov IRTC «Eye Microsurgery». In all cases restriction fragment length polymorphism analysis was performed. The frequency of TNF-308 GA and IL10-1082 GG genotypes was higher in AMD patients than in the controls, while the TNF-308 АA minor genotype has proved protective against the disease. Moreover, AMD has been found to be positively related to 48 genotypic combinations and negatively - to 32 (with specificity as high as 98-99%). The odds ratio was also higher in combination analysis as compared to monogenotypes. Complex genetic analysis of cytokines gives an idea of the balance of proinflammatory and anti-inflammatory cytokines in AMD and, therefore, plays an important role in studying the disease pathogenesis and exploring therapeutic options.

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.

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.

Cytokine Gene Polymorphisms in Patients With Interstitial Lung Disease: Gender Differences

PURPOSE: The aims of the present case-control study were to examine polymorphisms in the interleukin-6 (IL-6), IL-10, transforming growth factor (TGF)-β 1, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ genes in patients with ILD, compared to healthy controls.

Th1/Th2 cytokine gene polymorphisms in patients with idiopathic pulmonary fibrosis

We investigated 30 patients with idiopathic pulmonary fibrosis (IPF) and 103 healthy volunteers for the cytokines polymorphisms of the IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, tumor necrosis factor-alpha, interferon-gamma, transforming growth factor-beta, IL-1beta, IL-2, IL-4, and IL-4RA genes. The strongest correlation of a genotype with the disease was found for gene polymorphisms at the promotor region of IL-4, where the CT genotypes at the positions (-590) and (-33) were more frequent in the IPF group (P < 0.0001, P(corr) < 0.0022; vs P < 0.0001, P(corr) < 0.0022). Our results support the idea of the pathogenic role of cytokine gene polymorphisms in the etiology and pathogenesis of IPF, with emphasize on the IL-4 promotor gene polymorphisms.

The cytokine gene polymorphisms in patients with chronic kidney graft rejection

Chronic allograft rejection remains an important cause of morbidity after kidney transplantation. The aim of the study was to examine the association between IL-2, IL-6 and TNF-α promoter polymorphisms and chronic kidney allograft rejection. The study included 64 patients with long-term stable graft function and 62 with chronic allograft nephropathy. Among patients with chronic allograft nephropathy a statistically significant prevalence of the IL-6 CC genotype associated with low IL-6 expression was observed ( p<0.01, OR 3.18; 95% CI 1.27–8.15). There were no statistically significant differences in distribution of IL-2 and TNF-α genotypes between patients with stable graft function and chronic allograft rejection. The results of present study suggest that the genetically determined low IL-6 production may be the risk factor of chronic allograft nephropathy development.

Cytokine gene polymorphisms in patients infected with hepatitis B virus.

Cytokines play a key role in the regulation of the immune response. The maximal capacity of cytokine production varies among individuals and correlates with the polymorphism in the cytokine gene promoters. The aim of this study was to characterize gene polymorphism in patients with chronic hepatitis B virus (HBV) infection and to determine the different patterns in patient subgroups. The study population consisted of 77 patients with chronic HBV infection (23 low-level HBV replicative carriers, 23 compensated high-level HBV replicative carriers, 21 decompensated liver transplant candidates, and 10 patients with documented hepatocellular carcinoma). The genetic profile of five cytokines was analyzed by polymerase chain reaction-sequence-specific primer (SSP), and subjects were genotyped as high or low producers of tumor necrosis factor-alpha and interleukin (IL)-6, and as high, intermediate, or low producers of transforming growth factor-beta(1), interferon (IFN)-gamma, and IL-10 based on single nucleotide substitutions. The control group included 10 healthy individuals who recovered from HBV infection and 48 healthy controls. A highly statistically significant difference in the distribution of the IFN-gamma gene polymorphism (at position +879) was observed between patients with chronic HBV infection and controls. The majority of the patients (65.2%) exhibited the potential to produce low levels of IFN-gamma (A/A genotype) compared with 37.5% of the control group (p = 0.003). Healthy individuals who recovered from HBV infection had a similar distribution of IFN-gamma gene polymorphism as the healthy controls. No statistically significant difference in IFN-gamma production was found between patients with low- and high-level HBV replication and between compensated and decompensated patients. There was also no statistically significant difference in the genetic ability to produce tumor necrosis factor-alpha (at position -308), IL-6 (at position -174), IL-10 (at position -1082, -819, and -592), and transforming growth factor-beta(1) (at position +10 and +25). These findings suggest an association between the genetic ability to produce low levels of IFN-gamma and the susceptibility to develop chronic HBV infection.

Cytokine gene polymorphisms in patients infected with hepatitis B virus

Objective Cytokines play a key role in the regulation of the immune response. The maximal capacity of cytokine production varies among individuals and correlates with the polymorphism in the cytokine gene promoters. The aim of this study was to characterize gene polymorphism in patients with chronic hepatitis B virus (HBV) infection and to determine the different patterns in patient subgroups. Methods The study population consisted of 77 patients with chronic HBV infection (23 low-level HBV replicative carriers, 23 compensated high-level HBV replicative carriers, 21 decompensated liver transplant candidates, and 10 patients with documented hepatocellular carcinoma). The genetic profile of five cytokines was analyzed by polymerase chain reaction–sequence-specific primer (SSP), and subjects were genotyped as high or low producers of tumor necrosis factor-α and interleukin (IL)-6, and as high, intermediate, or low producers of transforming growth factor-β 1, interferon (IFN)-γ, and IL-10 based on single nucleotide substitutions. The control group included 10 healthy individuals who recovered from HBV infection and 48 healthy controls. Results A highly statistically significant difference in the distribution of the IFN-γ gene polymorphism (at position +879) was observed between patients with chronic HBV infection and controls. The majority of the patients (65.2%) exhibited the potential to produce low levels of IFN-γ (A/A genotype) compared with 37.5% of the control group ( p = 0.003). Healthy individuals who recovered from HBV infection had a similar distribution of IFN-γ gene polymorphism as the healthy controls. No statistically significant difference in IFN-γ production was found between patients with low- and high-level HBV replication and between compensated and decompensated patients. There was also no statistically significant difference in the genetic ability to produce tumor necrosis factor-α (at position −308), IL-6 (at position −174), IL-10 (at position −1082, −819, and −592), and transforming growth factor-β 1 (at position +10 and +25). Conclusion These findings suggest an association between the genetic ability to produce low levels of IFN-γ and the susceptibility to develop chronic HBV infection.

Cytokine gene polymorphism in patients with graft-versus-host disease

Cytokine gene polymorphism in patients with graft-versus-host disease