Investigation of IL-1 Beta, IL-1 Receptor Antagonist and IL-8 Gene Polymorphisms in Patients with Chronic Hepatitis B and C

WOS: 000336195500008PubMed: 24819264The host immune response is closely related to the prognosis of disease and viral persistence in hepatitis B (HBV) and hepatitis C virus (HCV) infections. Althought it is well known that cytokines and genetic factors play important roles in the pathogenesis of chronic HBV and HCV infections, the underlying mechanisms are not fully understood. This study was conducted to determine the role of interleukin (IL)-1 beta, IL-1 receptor antagonist (1L-1RA) and IL-8 gene polymorphisms in chronic hepatitis B and C infections. A total of 361 subjects, 171 with chronic hepatitis B (62 female, 109 male; age range: 18-74 yrs) and 104 with chronic hepatitis C (63 female, 41 male; age range: 25-79 yrs), and a control group of 86 healthy subjects (41 female, 45 male; age range: 18-72 yrs) were included in the study. Following the DNA extractions from peripheral blood leukocytes of the study groups, single nucleotide polymorphisms of 1L-1 beta -31, -511, +3954; IL-1RA and IL-8 -251, -353, -738, -845 gene regions were investigated by using specific primers with real-time PCR method. It was found that the genotype frequency of IL-8 -251 AT (OR: 7.895, p= 0.003) and IL-8 -738 TA (OR: 6.317, p= 0.007) in patients with chronic hepatitis B and the genotype frequency of IL-1 beta -31 CT (OR: 6.757, p= 0.001), IL-1 beta -511 CT (OR: 4.060, p= 0.004), IL-8 -251 AT, (OR: 13.622, p= 0.001), IL-8 -738 TA (OR: 14.058, p= 0.001), and IL-8 -845 TC (OR: 2.539, p= 0.004) in patients with chronic hepatitis C was significantly higher than the control group. When the allelic frequency was compared between chronic hepatitis B patients and the control group, it was determined that IL-1 beta +3954 T allel increased the disease risk 1.5 times (p 0.05). In conclusion, IL-1 beta -31, -511 and IL-8 -251, -738, -845 gene polymorphisms may play a role in the chronicity of hepatitis B and C infection. In order to determine the importance of this cytokine polymorphisms in hepatitis B and hepatitis C virus infections, large-scale studies with different patient groups such as carriers, chronic hepatitis, cirrhosis, and hepatocellular carcinoma should be conducted to elucidate the molecular mechanisms underlying the disease process

A functional polymorphism rs4938723 in the promoter of miR-34b/c is associated with an increased risk of lung cancer: A functional polymorphism rs4938723 in the promoter of miR-34b/c

Background: The expression level of some microRNAs (miRNAs) in lung cancer has been associated with an increased risk of cancer. miRNAs play a substantial role in the pathogenesis of human cancers. Because of that, miRNA polymorphisms can be important for carcinogenesis. MiR-34 is a family of miRNAs known to have reduced levels of expression in lung cancer and other human cancers (pancreas, colon). It functions like tumor suppressor and targets oncogenes like MET, RET, and RAB43. Also miR-125 family is related with many cancer types and targets P53, BCL2, VEGF, and EGFR

Functional association of interleukin-18 gene-607 C/A promoter polymorphisms with endometriosis

WOS: 000285411600076PubMed: 20797704This study evaluated for the first time the relationship between interleukin-18 (IL-18) C607A genotypes and endometriosis in 135 women with endometriosis and 84 controls. In the study population, IL-18 -607*A homozygote and A allele were positively correlated with the risk of developing endometriosis or the stage of endometriosis. (Fertil Steril (R) 2011; 95:298-300. (c) 2011 by American Society for Reproductive Medicine.

Investigation of the Association between Chronic Hepatitis B and C Infection and Interleukin 2 (-330) Gene Polymorphism

WOS: 000386047900002Objective: Cytokines has an important role in the immunopathogenesis of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Interleukin-2 (IL-2) secreted by Th1 cells which plays an important role in regulating both in activation of the immune system and homeostasis, is a cytokine having a wide spectrum of effects on the immune system. Although there are many studies investigating the relationship between IL-2-330 gene polymorphism and diseases, a few studied was found to investigate the role in the immunopathogenesis of HBV and HCV infections of this cytokine polymorphisms. This study was aimed to determine the relationship between IL-2-330 gene polymorphisms and chronic hepatitis B and C infections. Methods: A total of 139 patients with chronic hepatitis B, 101 patients with hepatitis C and 87 healthy subjects as control groups were included into this study. Approximately 2 ml of blood from patients and control groups were taken into tubes containing EDTA, and genomic DNA was isolated using DNA isolation kit. Single nucleotide polypmorphsim from the obtained DNAs was investigated using the polymerase chain reaction-confronting two-pair primers (PCR-CTPP) methods. Results: The genotype frequencies of IL-2-330 TT, GT, GG were detected as 23.7%, 53.2%, 23% in patients with chronic hepatitis B and 27.6%, 50.6%, 21.8% in control groups, respectively (p>0.05). The frequencies of TT, GT, GG genotypes were found to be 34.7%, 56.4%, 8.9% in patients with chronic hepatitis C and 27.6%, 50.6%, 21.8% in control group, respectively. GG genotype frequency was significantly lower in patient groups with hepatitis C compared with the control group (p0.05). The frequencies of T and G alleles were found to be 69.4%, 30.6% in patients with chronic hepatitis C and 52.9%, 47.1% in control groups, respectively (p<0.05). Conclusion: In our study while there was no statistically significant relationship between chronic hepatitis B and IL-2-330 gene polymorphisms, significant association was found between GG genotype and chronic hepatitis C. According to our findings the GG genotype in the-330 position of IL-2 gene may be preventive effect in chronicy of hepatitis C in Turkish population, however, further research can contribute to clarify the issue

Relationship Between TLR2 and TLR4 Gene Polymorphisms with Psoriasis

WOS: 000429662600006Objective: Psoriasis is a common, chronic and recurrent disease which can affect skin and also joints. Although the etiopathogenesis of psoriasis has not precisely determined, the most supported mechanism is inflammation triggered by any factor. Toll like receptors (TLRs) family described in recent years is known to play a critical role in host immunity against a wide variety of pathogens. In our study, we aimed to reveal possible relationships of some TLR gene polymorphisms with psoriasis in this patient group. Methods: A hundred patients who diagnosed with psoriasis and 173 healthy controls were included in the study which known to be without inflammatory disease, TLR2 gene Arg677Trp, Arg753Gln, -196-174 del and TLR4 gene Asp299Gly, Thr399Ile polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism method, patient and control groups were compared in terms of gene polymorphisms mentioned. Results: In this study, it was determined psosiasis has a statistically significant relationship with GA genotype and A allele in TLR2 Arg753Gln polymorphism. Furthermore, when the patient and control groups were compared for -196-174 del gene polymorphism, it was determined that ins/del genotype had a protective effect. Conclusion: We think that variant alleles in the TLR2 gene may play an important role in the molecular etiopathogenesis of psoriasis

Investigation of the Association Between Chronic Hepatitis B and C Infections and TNF-alpha(-308) Gene Polymorphism

WOS: 000378184000007PubMed: 27175496Cytokines and genetic factors play important roles in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) infections. Variations in cytokine genes may effect the gene expression and may lead to changes in the clinical manifestations of diseases. One of the single nucleotide polymorphisms in the promoter region of tumor necrosis factor-alpha (TNF-alpha) gene is the polymorphism at -308. position which was investigated in many studies by means of its relationship between CHB and CHC infections, however their results are incompatible. Furthermore, there is no sufficient data on this subject in our country. This study was aimed to determine the relationship between TNF-a(-308) gene polymorphism with CHB and CHC infections. A total of 271 patients with chronic hepatitis and 181 healthy subjects were included in the study. Of them 167 were CHB cases (67 female, 100 male; age range 18-74 years, mean age: 40.23 +/- 13.09) and 95 controls for CHB group (46 female, 49 male; mean age: 36.41 +/- 15.0 years), while 104 were CHC cases (63 female, 41 male; age range: 25-79 years, mean age: 52.8 +/- 12.6) and 86 controls for CHC group (41 female, 45 male; mean age: 36.4 +/- 14.9 years). After the isolation of genomic DNA from blood samples of the patient and control groups, TNF-alpha(-308)G/A (rs 1800629) polymorphism was investigated by using the real-time polymerase chain reaction from the obtained DNAs. Among CHB group, TNF-alpha(-308) GG, GA, AA genotypes were detected in 126 (75.4%), 38 (22.8%) and 3 (1.8%) of the patients, respectively, while these numbers were 84 (88.4%), 11 (11.6%) and 0 (0%) in control group, respectively. Among CHC group, TNF-a(-308) GG, GA, AA genotypes were detected in 37 (35.6%), 28 (26.9%) and 39 (37.5%) of the patients, respectively, while these numbers were 38 (44.2%), 8 (9.3%) and 40 (46.5%) in control group, respectively. The frequency of GA genotype was significantly higher in both patient groups compared to the control groups (p=0.024 for CHB and p= 0.006 for CHC). When the distribution of allele frequencies of TNF-alpha(-308)G/A polymorphism was evaluated in the patients and control groups, it was noted that G allele was found to be high in CHB patients comparing with controls (94.2% vs 86.8%), however A allele was identified to be lower than controls (5.8% vs 13.2%) (p= 0.008). In contrast, there was no significant difference in terms of allele frequency compared with CHC patients and the control group (p= 0.969). In conclusion, our data in accordance with the results of many studies in literature, determined that TNF-alpha(-308) polymorphisms can influence the chronicity of hepatitis B and C infections. Further studies on this subject would contribute to the elucidation of the molecular mechanisms of chronic hepatitis B and C diseases

Variant Analysis of the Sirtuin (SIRT1) Gene in Multiple Sclerosis

WOS: 000327752700006Objective: Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. Sirtuin 1 (SIRT1) is a neuroprotective enzyme in MS patients. The aim of our study was to investigate the relationship between a genetic variant of SIRT1 and MS. Design: Controlled prospective study Setting: Department of Neurology, Bulent Ecevit University Medical Faculty, Zonguldak, Turkey Subjects and Methods: We determined SIRT1 genotypes by polymerase chain reaction (PCR) and confronting two-pair primers (CTPP) methods in 93 MS patients and 100 healthy controls Intervention: For genetic analysis, 5 ml of venous blood was drawn from each patient into tubes containing EDTA Main Outcome Measures: SIRT1 gene polymorphisms and recorded expanded disability status scale (EDSS) for MS patients Results: We found a significant difference between the rs2273773 polymorphism of the SIRT1 gene of MS and the control group (p = 0.011). We also found an association between MS disease and the haplotypes of rs7895833, rs7069102 and rs2273773 polymorphisms. Conclusion: We have shown that rs2273773 polymorphism of the SIRT1 gene might be a risk factor for MS disease in the Turkish population. Also, additional studies are needed to clarify the role of the SIRT1 gene in the pathogenesis of MS disease

The relation of PON1-L55M gene polymorphism and clinical manifestation of Behcet's disease

Purpose: Behçet's disease is a multisystem disease characterized by recurrent oral and genital ulcers, relapsing uveitis, mucocutaneous, articular, gastrointestinal, neurologic, and vascular manifestations. Paraoxonase is believed to play an important role in protection of LDL and HDL particles from oxidation, in antioxidant effect against lipid peroxidation on cellular membranes, and in anti-inflammatory process. Lipid peroxidation and free oxygen radicals have been thought to play a role in pathogenesis of BD. The association of paraoxonase gene polymorphisms with Behçet's Disease in a group of Turkish patients with clinical manifestations and healthy controls has been investigated. Patients and Methods: Paraoxonase (PON-1-L55M) gene polymorphism was investigated in 50 Behcet patients and 50 healthy individuals with a PCR/RFLP method. Results: There were significant differences between patients and the control group in allele frequencies of the PON1 L55M polymorphism (p=0.04). Also, when patients were compared with the control group according to clinical manifestations, this statistical significance was getting sharper. Compared with the PON55 L allele, the M allele was associated with greater than 3.5 fold (OR 3.5, 95% CI 1.3-8.9) increased risk of ocular (OR 2.4, 95% CI 1.1-5.3), 2.4 fold joint and 3.1 fold (OR 3.1, 95% CI 1.1-8.4) central nervous system manifestations of BD. Conclusion The PON L55M gene polymorphism seemed to play a role in the pathogenesis of BD

The role of forkhead box class O3A and SIRT1 gene variants in early-onset psoriasis

Background: Psoriasis is a chronic inflammatory skin disorder, which is characterized by a heightened immunological response. Although the immunogenetics of this chronic inflammatory disorder is poorly understood, its expression is known to be dependent on proinflammatory cytokines. It is known that two distinct subtypes of chronic plaque psoriasis: Early-onset psoriasis (EOP) before the age of 40 years and late-onset psoriasis after the age of 40 years. Forkhead box class O3A (FOXO3A) is a transcription factor, which plays an important role in cell-cycle regulation, apoptosis, oxidative stress, and DNA repair. The silent information regulator (SIRT) is thought to have a role in skin disorders, including psoriasis, that are characterized by hyperproliferation and inflammation. Aim: The aim of this study was to investigate FOXO3A and SIRT1 gene polymorphisms in EOP. Methods: The study group consisted of 142 EOP patients and 123 unrelated healthy controls. FOXO3A polymorphisms were determined using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. SIRT1 gene polymorphisms were determined by PCR-confronting two-pair primers methods. Results: The FOXO3A rs4946936 and SIRT1 rs7069102 gene polymorphisms were positively correlated with EOP and disease severity. The GG genotype frequency of SIRT1 rs7069102 gene polymorphisms was increased in severe EOP. The CC frequency of FOXO3A rs4946936 was increased in EOP with nail disorders. Conclusion: The rs7069102 gene polymorphism of SIRT1 and rs4946936 polymorphism of FOXO3A are associated with early onset psoriasis; this may be responsible for increased keratinocyte proliferation in the pathogenesis of psoriasis and disease severity

Association Analysis of CHRNA4 Gene Polymorphisms and Levels of Marker of Oxidative DNA Damage and Oxidative Stress in Migraine Patients

WOS: 000328090600001Aim: Migraine is a primary headache syndrome which has been a genetic factor in quite complex etiopathogenesis. The mechanisms underlying the migraine have not been clearly enlightened. The aim of our study is to investigate the relationship between polymorphisms of CHRNA4 gene and migraine and determined to oxidative DNA damage and oxidative stress with detection of 8-oxo2dG and AOPP levels in plasma of patients with migraine. Methods: In our study, DNA was obtained from migraine patients (n=79) and unrelated healthy persons (n=68). Alleles and genotypes of CHRNA4 gene polymorphisms (rs1044394, rs1044393) were determined with PCR and RFLP methods. Also, 8-oxo2dG and AOPP levels were measured in plasma of migraine patients. Results: As a result, we were found a significant relationship between rs1044394 polymorphism of CHRNA4 gene and migraine patients without aura (p <0.05). Also, it was shown a significant association between rs1044394 polymorphism of CHRNA4 gene and smoker migraine patients (p <0.05). As an interesting, 8-oxo2dG levels in migraine patients were determinate significantly lower than healthy controls (p <0.05). Conclusions: According to our results, CHRNA4 gene may be important for migraine disease. Also, 8-oxo2dG levels in plasma of patients with migraine who have take medicine treatment might be decreased. This situation may show that drug therapy for migraine may reduce oxidative stress.scientific research projects unit of Mugla Sitki Kocman UniversityMugla Sitki Kocman University [BAP10/48]This study was supported by scientific research projects unit of Mugla Sitki Kocman University (BAP10/48). We would you like to thank to Prof. Dr. Aynur OZGE for her helps about manuscript editing