Could NCOA5 a novel candidate gene for multiple sclerosis susceptibility?

BACKGROUND: Multiple sclerosis (MS) is an inflammatory immune-mediated demyelinating disease that causes a challenging and disabling condition. Environmental and genetic factors play a role in appearing the state of the disease. Recent studies have shown that nuclear cofactor genes may play a role in the pathogenesis of MS. NCOA5 is a nuclear receptor coactivator independent of AF2 that modulates ERa-mediated transcription. This gene is involved in the pathogenesis of diseases such as psoriasis, Behcet's disease, and cancer. METHODS AND RESULTS: We investigated the relationship between the rs2903908 polymorphism of the NCOA5 gene and MS among 157 unrelated MS patients and 160 healthy controls by RT-PCR. The frequencies of the CC, CT, and TT genotypes were 19.87%, 37.82%, and 42.31%, respectively, for the MS group and 5.63%, 43.75%, and 50.62%, respectively, for the control group. The CC genotype and the C allele were found to be significantly higher in the patient group (the p values were 0.0002 and 0.003, respectively). CONCLUSIONS: The fact that the CC genotype was found to be significantly higher in the patient group compared to the control group (p = 0.0002) and that it had a statistically significantly higher OR value (OR, 95% CI = 4.16, 1.91-9.05) suggests that the C allele may recessively predispose to MS for this polymorphism. These results suggest for the first time that the NCOA5 gene may have an effect on the occurrence of MS through different molecular pathways, which are discussed in the manuscript.

Factors related to fatalities and clinical progression of Crimean-Congo hemorrhagic fever patients and the effects of IL 28-B gene polymorphism.

Mortality rates of Crimean-Congo hemorrhagic fever (CCHF) vary from 5% to 80%. However, there is no clear information available about why this disease is fatal for some people while others recover. In this study, the factors related to fatalities and serious clinical progression of CCHF patients and the correlation between serious prognosis and IL 28-B gene polymorphism were investigated. The study included 107 patients with a preliminary diagnosis of CCHF, and the patients were found positive for CCHFV RNA based on polymerase chain reaction (PCR) analysis. The IL 28-B rs12979860 polymorphism was identified by PCR "restriction fragment length polymorphism" (PCR-RFLP) analysis using blood samples from the patients. In addition to the IL 28-B analysis results, a variety of data along with laboratory records obtained during the hospital stay were evaluated using statistical analysis. Of the 107 cases, nine were fatal (8.4%), while the other patients recovered and were discharged. Twenty-four patients had the CC genotype (22.43%), 64 had the CT genotype (59.81%), and 19 had the TT genotype (17.76%). Of the nine patients who died, three had the CC genotype (33.33%) and six had the CT genotype (66.67%). None of the patients who died had the TT genotype. Symptoms and findings of diarrhea, abdominal pain, hemorrhage, and rash were more common in fatal cases than in non-fatal cases. The IL 28-B rs12979860 polymorphism was not found to have a statistically significant correlation with fatality or symptoms indicating serious clinical progression in CCHF patients. As has been observed in previous studies, our study showed that leukocytosis, abdominal pain and diarrhea were more common in fatal cases.

The possible role of CCR5Δ32 mutation in Crimean-Congo hemorrhagic fever infection.

Crimean-Congo hemorrhagic fever infection (CCHF) is a viral zoonosis. The pathogenesis of this disease has not been established so far, however, cytokines account for its progression and outcome. The aim of the present study is to investigate the association between chemokine receptor 5 (CCR5) gene Δ32 mutation and pathogenity, severity, and mortality of CCHF. This case-control study included 133 CCHF patients diagnosed by detection of CCHV RNA positivity and 97 healthy control subjects. CCR5 gene Δ32 mutation analyzed by polymerase chain reaction (PCR) method. The results were compared by using SPSS 16.0 and WINPEPI software's. The genotype distribution and allele frequency of the CCR5Δ32 were statistically different between the patients and the control group (P = 0.017; OR: 4.98 95% CI = 1.65-14.99 and P = 0.019; OR:4.76 95%CI = 1.30-17.50, respectively). CCR5/CCR5 (W/W) genotype and W allele of CCR5 gene were more common in patient group than in controls. There was no significant difference in severe and mild cases with regard to genotype distribution and allele distribution of CCR5Δ32 mutation (P >0.05). These results suggest that the CCR5 gene and its product might play a role in the pathogenesis of CCHF disease. Future studies will help us to uncover the exact role of CCR5 in the pathogenesis and prognosis of CCHF and to treat the disease.

Associations of rs4810485 and rs1883832 polymorphisms of CD40 gene with susceptibility and clinical findings of Behçet's disease.

There are evidences that besides geographic tendency, interactions between genetic and environmental factors play an essential role in the pathogenesis of Behçet's disease (BD). In this study, we have evaluated the associations between rs4810485 and rs1883832 single nucleotide polymorphism (SNP)s of CD40 gene with the susceptibility and clinical findings of BD. Two hundred and eighty-five patients with BD and 225 age-matched healthy controls were enrolled in this study. The clinical findings of patients were noted. The distributions of genotypes, alleles, combined genotypes and haplotypes of these two SNPs in BD patients were compared with those in healthy controls. In further evaluation, we evaluated the patients with and without any of clinical findings with regarding to distribution of genotypes and alleles of these two SNPs. There was no significant difference concerning frequencies of genotypes, alleles, combined genotypes and haplotypes of rs4810485 and rs1883832 between patients and controls (p > 0.05 for all). Frequency of GT genotype of CD40 rs4810485 polymorphism was found to be significantly higher in patients with skin lesions (p < 0.05, OR 1.65, 95 % CI 1.02-2.64). Also, we have found significantly higher frequencies of CC genotype and C allele of CD40 rs1883832 polymorphism in patients with genital ulcers (p < 0.05 for both, OR 2.30, 95 % CI 1.07-4.94 and OR 1.78, 95 % CI 1.06-2.97, respectively). However, these significances were disappeared after Bonferroni correction. We suggest that differences in the expression levels of CD40 because of different genotypes of these two SNPs may take part in the development of skin lesions or genital ulcers in patients with BD.

Association analysis of three ABCB1 (MDR1) gene variants (C1236T, G2677A/T and C3435T) and their genotype/haplotype combinations with the familial Mediterranean fever.

1. Familial Mediterranean fever (FMF) is considered an autosomal recessive disorder, associated with a single gene named Mediterranean fever (MEFV). The aim of this study was to perform genotyping and haplotyping analysis of the multidrug resistance (ATP-binding cassette, subfamily B, member 1 - ABCB1) gene in FMF patients. 2. Three ABCB1 gene polymorphisms (C1236T, G2677T/A and C3435T) were analyzed in 309 FMF patients and 250 healthy control subjects. All subjects were genotyped by PCR-restriction fragment length polymorphism analysis, and statistical analysis was performed using the Arlequin 3.1.1 and SPSS 16.0 software packages. 3. The CT genotype frequency of the C3435T polymorphism (p = 0.003), the CT-GT-CT (C1236T-G2677T/A-C3435T) triple genotype (p = 0.001) and the C-G (C1236T-G2677T/A) haplotype (p = 0.030) were more common in the FMF patients. The CT-GG-CC triple genotype and T-G-C, C-T-T and T-G-T haplotypes (C1236T-G2677T/A-C3435T) were higher in the control subjects (p = 0.011, 0.001, 0.009 and 0.000, respectively). The CT-GG binary genotype and C-T and T-G haplotypes for C1236T-G2677T/A polymorphisms may have a high degree of protective effect against FMF (p = 0.0005, 0.002 and 0.000, respectively). 4. Our study showed that genotypes and haplotypes of ABCB1 gene polymorphisms may affect patients' FMF susceptibility.

Investigation of MIF gene promoter variations and their haplotypes in the Alzheimer disease in Turkish population.

In Alzheimer's disease, which is characterized by amyloid plaques and neurofibrillary tangles in the brain tissue, many components such as acute phase proteins, cytokines, and proteases contribute to the progression of the disease or are part of the pathological process. The macrophage migration inhibitory factor (MIF) gene encodes a cytokine, which is secreted by lymphocytes, and has a role in the pathogenesis of autoimmune/inflammatory diseases such as rheumatoid arthritis. The purpose of this study to investigate the association between Alzheimer disease and MIF gene promoter polymorphisms. The 205 patients with Alzheimer disease (AD) and 130 age-sex matched healthy individuals were investigated in terms of MIF -173 G/C and MIF -794 CATT polymorphisms. The genotyping of MIF -173 G/C was determined using the RT-PCR method. MIF-794 CATT polymorphism was analyzed using PCR and DNA Sequencing. In terms of binary genotypes and haplotypes, the 5/5-GC (p = 0.004), 6/7-GG (p = 0.02) and, 6/6-GG (p = 0.026) binary genotypes, and 5-C (p = 0.003), 7-G (p = 0.026) and 6-G (p = 0.025) haplotypes were differed significantly between the patients and the controls. This is the first study investigating the relationship between AD and MIF in terms of different genotypes, haplotypes and, alleles. The fact that the binary genotype and allele distributions are significantly different between the patient and control group, suggests that this MIF variants may play a role in the pathogenesis of AD.

DD genotype of ACE gene I/D polymorphism is associated with Behcet disease in a Turkish population.

Behcet's disease (BD) is a chronic, multi-systemic and inflammatory disorder. The local renin-angiotensin system (RAS) in the vessel wall plays a role in the endothelial control and contributes to inflammatory processes. Angiotensin-converting enzyme (ACE) is the regulatory component of the RAS. This study was conducted in Turkish patients with BD to determine the frequency of I/D polymorphism genotypes of ACE gene. Genomic DNA obtained from 566 persons (266 patients with BD and 300 healthy controls). ACE gene I/D polymorphism genotypes were determined using polymerase chain reaction using I and D allele-specific primers. There was statistically significant difference between the groups with respect to genotype distribution (p < 0.001). This study is the largest study in Turkish population that ACE gene I/D polymorphism investigated in BD. As a result of this study, ACE gene I/D polymorphism DD genotype could be a genetic marker in BD in Turkish study population.

Investigation of circadian rhythm gene Per3 in diabetic neuropathy.

PURPOSE: Diabetic neuropathy (DN) is a serious complication of diabetes that affects peripheral and autonomic nerves, and it has been linked to irregularities in circadian rhythm. Several studies have demonstrated that disruptions in circadian rhythm and changes in expression of rhythm genes may play a role in the development and progression of diabetes, including the development of DN. METHODS: In this study, the association between the VNTR polymorphism of the PER3 gene and diabetic neuropathy was investigated. The study included 84 patients with diabetes, 220 patients with diabetic neuropathy, and 218 healthy individuals as the control group. RESULTS: Upon analyzing the data from the study, it was found that there was no significant difference in the PER3 VNTR polymorphism between the diabetic neuropathy patients, diabetes and control groups. However, there was a significant difference observed between the control group and the diabetes group, particularly in terms of the 5/5 genotype and 5 alleles. Moreover, a significant difference was observed between the patient group and the control group (p < 0.05). CONCLUSIONS: In conclusion, first in the world, the relationship between PER3 gene VNTR polymorphism and diabetic neuropathy and diabetes, was investigated. Our results showed that PER3 may be associated with diabetes but not with diabetic neuropathy.

Association between the methylene tetrahydrofolate reductase gene C677T mutation and colchicine unresponsiveness in Behcet's disease.

PURPOSE: Behcet's disease (BD) is a multisystemic immunoinflammatory disorder characterized by mucocutaneous, ocular, vascular, and central nervous system manifestations. The common methylene tetrahydrofolate reductase (MTHFR) gene C677T mutation is a known risk factor for thrombosis. The aim of this study was to investigate the MTHFR gene C677 mutation in patients with BD and evaluate if there was an association with clinical features, especially thrombosis, in a relatively large cohort of patients with BD. METHODS: The study included 318 patients with BD and 207 healthy controls. Genomic DNA was isolated and genotyped using PCR-based restriction fragment length polymorphism assay for the MTHFR gene C677T mutation. RESULTS: The genotype and allele frequencies of the C677T mutation showed a statistically significant difference between BD patients and controls (p=0.003 and p=0.001, respectively). There was also a significant association between C677T alteration and response to colchicine in BD patients (p=0.046). CONCLUSIONS: The results of this study showed that there was a high association between the MTHFR gene C677T mutation and BD. Stratification analysis according to clinical features for this disease did not reveal an association except response to colchicine that was shown to be influenced by the MTHFR C677T mutation.

Methylene-tetrahydrofolate reductase gene C677T and A1298C polymorphisms as a risk factor for Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a deadly viral disease. Methylene-tetrahydrofolate reductase (MTHFR) has an important role in folate metabolism, and also in the formation of new cells, DNA synthesis, repair and methylation. We aimed to examine the relationship between MTHFR gene C677T (Ala222Val, rs1801133) and A1298C (Glu429Ala, rs1801131) polymorphisms with CCHF in a Turkish population. Totally 273 participants were included in the current study. One hundred forty-one participants were CCHF patients and one hundred thirty-two participants were healthy controls. The polymerase chain reaction (PCR) and further restriction fragment length polymorphism (RFLP) assays were applied to determine the genotypes of MTHFR polymorphisms. We did not find any differences between the CCHF patients and healthy controls in terms of allele and genotype distributions of both the C677T and A1298C polymorphisms. In composite genotype analysis between different groups, the frequency of CT-AA composite genotype, which is formed by C677T-A1298C polymorphisms, was found to be significantly higher in Mild CCHF patients compared to both Severe CCHF patients and controls (p = 0.036 and p = 0.008, respectively). In conclusion, in this study, we found a relationship between CCHF and MTHFR gene polymorphisms. CT-AA composite genotype of MTHFR gene C677T and A1298C polymorphisms showed a predisposition to Mild CCHF.

Impact of Endothelial NOS VNTR Variant on Susceptibility to Diabetic Neuropathy and Type 2 Diabetes Mellitus.

PURPOSE: The aim of this study was to evaluate whether the VNTR intron 4b/4a variant in the eNOS gene is associated with type 2 diabetes mellitus (T2DM) and DPN. METHODS: A total of 598 subjects were enrolled in the study. eNOS VNTR 4b/4a variant was genotyped by polymerase chain reaction (PCR) method. RESULTS: eNOS VNTR intron 4b/4b genotype and b allele increased in patients with both DPN and T2DM compared healthy controls (p=0.0005, OR:1.94, p= 0.000002, OR:4.10, respectively). 4a/4b genotype was more prevalent in controls than in DPN and T2DM patients (p=0.00008, OR:0.46; p=0.000004, OR:0.24, respectively). eNOS VNTR b allele was more common in DPN patients and T2DM patients compared with controls (p=0.007, p=0.00002, respectively). CONCLUSION: The eNOS VNTR "4b/4b" homozygous genotype and hence "4b"allele as a genetic risk factor for T2DM and DPN, which may serve as a useful marker of increased susceptibility to the risk of these disorders.

Effects of Paraoxonase-1 variants on course of severity and mortality of Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever caused by Crimean Congo hemorrhagic fever virus (CCHFV). Paraoxonase-1 (PON1) is a high density lipoprotein (HDL)-binding protein which defense the body against oxidative stress. To investigate the role of the PON1 gene in CCHF, we screened the genotypes of two single nucleotide polymorphisms (Q192R [rs662] and L55M [rs854560]) in CCHF patients stratified according to course of severity and mortality by using PCR-based RFLP assay. Overall, 132 patients diagnosed as CCHF were enrolled in this study. The frequencies of the three genotypes and two alleles of Q192R and L55M polymorphisms didn't show any statistically significant differences in terms of mortality and disease severity (p > 0.05). Any statistically significant differences were not found between severe and mild and fatal and non-fatal CCHF patients according to seven composite genotypes (p > 0.05). When we analyzed the clinical characteristics of CCHF patients stratified according to PON1gene polymorphisms, any statistically significant differences were not also observed (p > 0.05). Our study showed no possible association between genotypes of PON1 gene Q192R and L55M polymorphisms and CCHF.

IL-1ß and IL-1Ra Variant Profiles in Turkish Patients with Diabetic Peripheral Neuropathy.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common complications of Type 2 diabetes mellitus (T2DM). This study was conducted to investigate the possible association between interleukin-1ß (IL-1ß) rs16944 /IL-1 receptor antagonist (IL-1Ra) VNTR variants and genetic susceptibility to DPN in a Turkish cohort. METHODS: A total of 200 subjects were enrolled in this study, 98 patients with DPN and 102 cases of age and sex-matched healthy controls. Genotyping was performed for all individuals using PCR-RFLP analysis. RESULTS: IL-1ß rs16944 CC genotype had a 3.20-fold increased risk for DPN (p=0.0003, OR=3.20, 95% Cl:1.72-5.96). IL-1ß rs16944 CT genotype was higher in healthy control than patients (p=0.004). IL-1ß rs16944 C allele was higher in the patient group compared to controls while T allele was lower in patients than controls (p=0.003). IL-1Ra VNTR a1/a1 and a2/a2 genotypes were lower in DPN patients while a1/a2 genotype was higher in patients (p=0.045). The patients carrying a1/T haplotype had decreased risk of DPN than control groups (p=0.004). The patients carrying a2/a2 genotype had lower HDL level (p=0.039). The subjects carrying a2/a2 genotype had higher total cholesterol level while the subjects carrying a1/a2 genotype had lower total cholesterol (p=0.026 and p=0.037, respectively). IL-1Ra a1 allele was associated with higher HDL level (p=0.041). CONCLUSION: Findings of this study indicated that the IL-1ß rs16944 and IL-1Ra VNTR variants are probably to be associated with susceptibility DPN risk in a Turkish cohort.

Association between Vitamin K Epoxide Reductase (VKORC1) -1639G>A Polymorphism and Osteoporosis in Postmenopausal Women.

Introduction: Osteoporosis is a common disease, and several factors contribute to its development. Recently, there has been increasing evidence that vitamin K (VK) plays a critical role in maintaining bone strength. Vitamin K serves as a co-factor for the γ-carboxylation of particular proteins to convert specific glutamic acid residues to γ-carboxyglutamic acid residues. This process involves two enzymes, γ-glutamyl carboxylase and vitamin K epoxide reductase (VKORC1). The number of studies investigating the effects of VKORC1 gene mutations on bone mineral density in postmenopausal osteoporosis patients is limited. The aim of this study was to investigate the relationship between the VKORC1 -1639G>A polymorphism and osteoporosis in postmenopausal Turkish women. METHODS: The study group consisted of 176 postmenopausal women with osteoporosis and 140 healthy postmenopausal women. The selection criteria for the healthy controls included non-osteoporotic bone mineral density (BMD) and similar demographic characteristics to the osteoporosis group. The genotyping of the VKORC1 -1639G>A polymorphism was conducted using the restriction fragment-length polymorphism method. RESULTS: We found that the genotype frequencies of the GG, GA and AA genotypes were 25.6, 64.2 and 10.2% in the patients and 33.6, 55.8 and 10.7% in the controls, respectively. In the patient and control groups, the genotype distribution of the studied locus was found to be non-compatible with Hardy-Weinberg equilibrium. We found a nonsignificant association between the -1639G>A polymorphism in the VKORC1 gene and osteoporosis in postmenopausal Turkish women. CONCLUSION: We have shown that the VKORC1 -1639G>A polymorphism is not a risk factor for postmenopausal osteoporosis.

Clinical significance of NCOA5 gene rs2903908 polymorphism in Behçet's disease.

Behçet's disease (BD) is an autoimmune multisystemic disease. The precise etiology of BD is not fully understood; however, it is thought that interactions between genetic and environmental factors play an essential role in its pathogenesis. The nuclear receptor coactivator-5 (NCOA5) gene encodes a coregulator for nuclear receptor subfamily 1 group D member 2 (NR1D2) and estrogen receptor 1 and 2 (ESR1 and ESR2). Also, the NCOA5 gene insufficiency leads to an elevated expression of IL-6, and increased levels of IL-6 were found to be related to the pathogenesis of BD. In this study, we aimed to clarify the impact of the NCOA5 rs2903908 polymorphism on susceptibility and clinical findings of BD. This study included 671 participants (300 BD patients and 371 healthy controls). The analyses of NCOA5 rs2903908 polymorphism was performed by using the TaqMan allelic discrimination assay. The frequency of TT genotype of the NCOA5 rs2903908 polymorphism was found significantly higher in BD patients compared to those in healthy controls (p=0.016, OR=1.46, 95 % CI=1.08-1.99). Also, the frequencies of CT genotype was observed significantly higher in BD patients with genital ulceration and uveitis than without genital ulceration and uveitis (p=0.002 and p=0.005, respectively). The most significant association was found between C allele frequencies of BD patients with and without uveitis (p=0.0001). Our study represents for the first time that the NCOA5 rs2903908 polymorphism seemed to be linked to BD susceptibility and clinical findings.

Investigation of CD40 gene rs4810485 and rs1883832 mutations in patients with recurrent aphthous stomatitis.

OBJECTIVES: Recurrent aphthous stomatitis (RAS) is a common painful disorder affecting oral health, mucosa and overall quality of life. The etiopathogenesis of RAS remains unclear. RAS shows a large genetic diversity among the patients. In present study, we investigated whether CD40 gene rs4810485 and rs1883832 are associated with RAS and its clinical findings in Turkish patients. MATERIALS AND METHODS: Genomic DNA obtained from 387 individuals (160 patients with RAS and 227 healthy controls) were used in the study. CD40 gene rs4810485 and rs1883832 mutations were determined by using polymerase chain reaction with the specific primers. RESULTS: There was no statistically significant difference between the groups with respect to genotype and allele distribution (p>0.05, OR 0.94, 95% CI 0.70-1.28, OR 1.01 95% CI 0.75-1.37, respectively). Additionally, there was no statistically significant difference in the combined genotype analysis of CD40 gene rs4810485 and rs1883832 mutations (p>0.05). CONCLUSIONS: According to our results, we found that CD40 gene mutations are not associated with RAS. We are convinced that CD40 gene mutations do not predispose to develop RAS in Turkish population. To our knowledge, this is the first study regarding CD40 gene rs4810485 and rs1883832 mutations investigated in RAS patients.

The IL4-VNTR P1 Allele, IL4-VNTR P2P2 Genotype, and IL4-VNTR_IL6-174CG P2P1-GG Genotype Are Associated with an Increased Risk of Brucellosis.

In this study, associations between IL-4, IL-6, and macrophage migration inhibitory factor (MIF) polymorphisms and susceptibility to brucellosis were investigated. Consecutive adult patients with no known treatment against brucellosis and who did not have any other autoimmune and/or chronic disorders, were included in this study (n = 120, Group I). Age and sex-matched controls who had no other autoimmune and/or chronic disorders were also included (n = 120, healthy volunteers, Group II). The IL4_P2P2 genotype, IL4_P1 allele, and IL4_variable number of tandem repeats (VNTR)_IL6-174CG compound genotype were found to be more frequent in the patient group than in control subjects. There were significant differences between the patients and controls with respect to the frequencies of the IL4_P2P2 genotype (77.5% versus 87.5%; p = 0.001; OR, 0.36; 95% confidence interval [CI], 0.21-0.62) and the IL4_P1 allele (12.1% versus 6.7%; p = 0.030; OR, 0.92; CI, 1.02-3.64). The IL4-VNTR_IL6-174CG compound genotype was also present at a significantly higher frequency in the patient group than in control subjects (11.7% versus 4.2%; p = 0.027, OR, 3.04; CI, 1.06-8.68). No statistically significant differences in the frequencies of the IL-6-174, MIF-173, IL-4_P1P1, and IL4_P2P1 genotypes were observed between patients and control subjects. The IL4_VNTR P1 allele, P2P2 genotypes, and IL4-VNTR_IL6-174CG P2P1-GG genotypes are common in southern Turkey, and carriers of these polymorphisms are susceptible to brucellosis.

Evaluation of MIF -173 G/C Polymorphism in Turkish Patients with Ankylosing Spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the spine and sacroiliac joints. Macrophage migration inhibitory (MIF) factor is a regulatory cytokine that inhibits random immune cell migration. MIF gene promoter polymorphisms play a role in the progression of several inflammatory disorders. AIMS: To investigate the relationship between the MIF gene -173 G/C single-nucleotide polymorphism (SNP) and AS. STUDY DESIGN: Cross-sectional study. METHODS: In this study, a total of 161 AS and 194 normal controls were recruited. The MIF gene -173 G/C SNP was analyzed by polymerase chain reaction using the restriction fragment length polymorphism method. RESULTS: There was no significant difference between groups in terms of genotype distribution (p>0.05). When wild-type G/G and G/C+C/C genotypes are compared in terms of clinical characteristics, there is a significant difference between the average age and the duration of disease in AS patients (p<0.05). CONCLUSION: No significant relationship between AS disease and MIF -173 G/C polymorphism was found. MIF -173 G/C polymorphism (C allele) may affect the time of onset and the duration of disease in AS patients.

Effects of interleukin (IL)-6 gene polymorphisms on recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is a common disease with oral ulceration in which cytokines are thought to play an important role. High levels of interleukin (IL)-6, a pro-inflammatory cytokine have been detected in the circulation of ulcer tissue. The purpose of the present study was to investigate if the IL-6 gene polymorphisms are associated with RAS or clinical characteristics of RAS in a cohort of Turkish population. 184 RAS patients and 150 healthy controls were included in the study. The genotypes of IL-6 gene -572G>C and -174G>C polymorphisms were determined using polymerase chain reaction based restriction fragment length polymorphism analysis. The genotype frequencies of -572G>C polymorphism showed statistically significant differences between RAS patients and controls (p = 0.01). Frequencies of GG + GC genotypes and G allele of -572G>C polymorphism were found higher in RAS patients (p = 0.0001, OR 10.8, 95 % CI 2.79-70.5; p = 0.0008, OR 2.06, 95 % CI 1.35-3.17, respectively). The genotype frequencies of -174G>C polymorphism also showed statistically significant differences between RAS patients and controls (p < 0.0001). Frequencies of GG genotype and G allele of -174G>C polymorphism were found higher in RAS patients (p < 0.0001, OR 4.87, 95 % CI 3.06-7.85; p < 0.0001, OR 3.82, 95 % CI 2.64-5.59, respectively). GG-GG combined genotype and G-G haplotype of -174G>C to -572G>C loci were also significantly higher in RAS patients (p < 0.0001 and p = 1.5 × 10(-8), respectively). After stratifying clinical and demographical characteristics of RAS patients according to IL-6 gene polymorphisms, an association was observed between family history of RAS and -174G>C polymorphism (p = 0.011). Susceptibility effects of both IL-6 gene -572G>C and -174G>C polymorphisms for RAS were observed. Further studies are necessary to prove the association of IL-6 gene polymorphisms with RAS.

Impact of Interleukin 28B Genotype on the Virological Responses in Chronic Hepatitis C Treatment.

BACKGROUND: Interleukin (IL) 28B single nucleotide polymorphisms may play a role in the clearance of hepatitis C virus (HCV). We aimed to evaluate the treatment response of chronic HCV infection patients to pegile interferon (pegIFN) and ribavirin treatment with regard to IL28B rs12979860 C/T polymorphism. METHODS: A total of 186 patients (mean age, 55.6 ± 10 years; 65.1% female) who underwent pegIFN and ribavirin treatment for chronic HCV infection were studied. We analyzed demographics, HCV genotype, baseline alanine aminotransferase (ALT) levels, histopathological data, viral load before treatment and at 4, 12, 24, 48, and 72 weeks from the treatment start, and IL28B genotype. IL28B polymorphism was genotyped using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in all the subjects. RESULTS: One hundred forty-five (86.8%) patients were infected with viral genotype 1b, and 13.2% were infected with viral genotype 4. The rates of C/C, C/T, and T/T genotypes were 22.6%, 52.7%, and 24.7% respectively. The percentage of patients with a viral load over 400,000 IU/mL was higher in the C/T group (P = 0.020). Of the patients, 44.6% provided sustained virological response (SVR) to pegIFN and ribavirin combination treatment. The frequency of T allele was 41% in patients with SVR, whereas 59% patients provided no response (P < 0.001). SVR was obtained in 66.7%, 42.9%, and 28.3% of CC, CT, and TT groups (P = 0.001). The rates of rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and SVR were higher in the CC group than other groups (P = 0.216, P < 0.001, P = 0.001, P = 0.001, respectively). The relapse and null response (NR) rates were higher in TT group and partial response rate (PR) was higher in CT group. CONCLUSIONS: IL28B rs12979860 C/T gene polymorphism affects the response to antiviral treatment in the patients with chronic HCV genotypes 1b and 4 infections.