Fibroblast growth factor-23 in patients with systemic sclerosis: A case–control study

AbstractBackgroundFibroblast growth factor-23 (FGF-23) is actively involved in phosphate homeostasis and skeletogenesis.Aim of the workTo assess the serum level of FGF-23 in systemic sclerosis (SSc) patients (both diffuse dSSc and limited lSSc subtypes) in order to find if it has a role in the pathogenesis of the disease and study its relation to the clinical manifestations.Patients and methodsThe study included 30 dSSc patients, 30 lSSc and 28 age and sex matched controls. In patients, clinical examination and laboratory investigations were performed and Medsger severity scale assessed. Serum FGF-23 was measured using ELISA.ResultsThe age of dSSc patients was 36.94±9.89years and the lSSc 38.36±10.04years. The serum FGF-23 level was 23.44±14.86pg/ml in dSSc patients, 20.01±13.92pg/ml in lSSc patients and 23.09±11.45pg/ml in the control (p=0.58). No significant difference in the FGF-23 level was found according to the presence of lung fibrosis (p=0.6). There was no significant difference in FGF levels among patients according to the severity (p=0.39). In SSc patients there was a significant correlation between FGF and serum phosphorus especially in dSSc patients (r=0.6, p=0.003). Serum urea significantly correlated with FGF-23 in those with dSSc (r=0.46, p=0.037). There was no significant difference in the FGF-23 levels (p=0.18) between those with a normal and impaired glomerular filtration rate.ConclusionThe mean serum level of FGF-23 in this study showed no significant difference between systemic sclerosis patients and their subtypes with the normal subjects. It seems to have no role in the clinical manifestations of the disease

A Meta-Analysis of Interleukin-8 -251 Promoter Polymorphism Associated with Gastric Cancer Risk

Background: Potential functional allele A/T single nucleotide polymorphism (SNP) of Interleukin 8 (IL-8) promoter-251has been implicated in gastric cancer risk. Methods: We aimed to explore the role of A/T SNP of IL-8-251 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Eighteen studies were ultimately eligible for the meta-analysis of IL-8- 251 A/T SNP. We adopted the most probably appropriate genetic model (codominant model). Potential sources of heterogeneity were sought out via stratification and sensitivity analyses, and publication biases were estimated. Results: Between IL-8-251 AA genotype with gastric cancer risk, statistically significant association could be noted with overall gastric cancer, evidently noted in Asians, witnessed in high quality subgroup, and apparently noted in intestinal-type gastric cancer. Conclusions: Our meta-analysis indicates that IL-8-251 AA genotype is associated with the overall risk of developing gastric cancer and may seem to be more susceptible to overall gastric cancer in Asian populations. IL-8-251 AA genotype is more associated with the intestinal-type gastric cancer. IL-8-251 AA genotype is not associated with Helicobacter Pylori infection status in our meta-analysis

Joint Effects of Febrile Acute Infection and an Interferon-γ Polymorphism on Breast Cancer Risk

BACKGROUND: There is an inverse relationship between febrile infection and the risk of malignancies. Interferon gamma (IFN-γ) plays an important role in fever induction and its expression increases with incubation at fever-range temperatures. Therefore, the genetic polymorphism of IFN-γ may modify the association of febrile infection with breast cancer risk. METHODOLOGY AND PRINCIPAL FINDINGS: Information on potential breast cancer risk factors, history of fever during the last 10 years, and blood specimens were collected from 839 incident breast cancer cases and 863 age-matched controls between October 2008 and June 2010 in Guangzhou, China. IFN-γ (rs2069705) was genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. We found that women who had experienced ≥1 fever per year had a decreased risk of breast cancer [ORs and 95% CI: 0.77 (0.61-0.99)] compared to those with less than one fever a year. This association only occurred in women with CT/TT genotypes [0.54 (0.37-0.77)] but not in those with the CC genotype [1.09 (0.77-1.55)]. The association of IFN-γ rs2069705 with the risk of breast cancer was not significant among all participants, while the CT/TT genotypes were significantly related to an elevated risk of breast cancer [1.32 (1.03-1.70)] among the women with <1 fever per year and to a reduced risk of breast cancer [0.63 (0.40-0.99)] among women with ≥1 fever per year compared to the CC genotype. A marked interaction between fever frequencies and the IFN-γ genotypes was observed (P for multiplicative and additive interactions were 0.005 and 0.058, respectively). CONCLUSIONS: Our findings indicate a possible link between febrile acute infection and a decreased risk of breast cancer, and this association was modified by IFN-γ rs2069705

The Association of Vitamin D Receptor Gene BsmI Polymorphism with Multiple Sclerosis in Iranian Patients

Abstract: Background & Aims: 1,25-dihydroxyvitamin D3 (1,25 (OH)2 D3), the biologically active form of vitamin D, exerts an immunosuppressive effect through binding to its specific nuclear receptor. The present case-control study was done to examine the possible association of BsmI polymorphism in vitamin D receptor gene (VDR gene) with severity of multiple sclerosis (MS). Methods: 267 Iranian patients with MS and 292 ethnically and sex matched controls were included in this study. BsmI polymorphism in VDR gene was assessed by PCR-RFLP method. Results: No differences in the allelic distribution were observed in the patients as compared to the controls. Also no difference in genotype distribution of VDR-BsmI polymorphism was observed between patients and controls (p=0.43). Conclusion: Considering the significance of vitamin D3 as an immune system regulator and its inhibitory effects on MS, investigation on other VDR gene polymorphisms is recommended. Keywords: Multiple sclerosis, Vitamin D, Polymorphism, Ira

Relation between C.32 A>T Polymorphism In TLR7 and Response to Treatment in Chronic HCV-Infection

ABESTRACT: Introduction & Objective: Hepatitis C virus (HCV)-infection leads to development of chronic hepatitis, liver cirrhosis and hepatoma. Both the liver damage and extrahepatic manifestation of HCV are immune-mediated. Since HCV is an RNA virus, a role for toll like receptor 7 (TLR7) in the immune response against HCV is likely. The aim of the present study was to determine the frequency of C.32T allele of TLR-7 in general and chronic HCV hepatitis, and its effect on treatment of HCV. Materials & Methods: This case –control study was carried out on 154 patients of chronic hepatitis C in 2008-2009. The patients were selected from referrals to Hepatitis clinic at Shahid Motahari Polyclinic affiliated to Shiraz University of Medical Sciences, Shiraz, Iran which had indication of treatment. The patients were randomly selected according to inclusion and exclusion criteria. Control group consisted of 225 healthy subjects. The frequency of c.32T allele of TLR-7 was determined in154 patients with chronic HCV-infection, and in 225 healthy controls. Treatment with interferon-alpha and ribavirin was performed after genotype determination. Sustained virologic response (SVR) and end treatment response (ETR) were determined and effect of c.32T allele of TLR-7 on outcomes of treatment was evaluated. Results: The frequency of c.32T allele of TLR-7 in patients with chronic hepatitis C was 15.33% in male, 14.67% in female and totally 15.2%. The frequency of c.32T allele of TLR-7 in healthy control group was 16.24% in male, 10.3% in female and totally 14.67%. The rate of Sustained Virologic Response (SVR) was 75%, but in patients that had c.32T allele of TLR-7, SVR was 55% (p=0.046). Conclusion: c.32A>T single nucleotide polymorphism of TLR-7, by impairment of TLR-7 function, can be considered among host factors that had unfavorable effect on response rate to treatment of patients with chronic HCV hepatitis. Keywords: Hepatitis C virus, Toll like receptor 7 (TLR7), Sustained Virologic Response, End treatment response (ETR

Determination of serum visfatin levels in patients with Behcet’s disease: a case–control study

Abstract Aim of the work: Behc¸et’s disease (BD) is an inflammatory, systemic and chronic disorder with unknown etiology affecting multiple systems. Visfatin is a new adipokine with insulinmimetic properties and pro-inflammatory function. The serum visfatin levels were evaluated in BD patients to investigate its role in the pathogenesis and clinical manifestations of the disease. Patients and methods: Forty BD patients were recruited from the Behc¸et’s disease clinic at Shiraz University of Medical Sciences in southern Iran and 40 healthy control subjects of matching age, sex and body mass index (BMI) were also included. Serum visfatin level was measured using ELISA. Results: The 40 BD patients included 16 males and 24 females. Seventeen had active clinical manifestations; 16 with oral ulcer, 5 with genital ulcer, 6 with arthritis and 2 with uveitis. The mean age of the BD patients was 34.95 ± 9.6 years and mean BMI was 23.98 ± 4.44. There were no significant differences between cases (5.05 ± 3.05 ng/ml) and controls (4.72 ± 2.84 ng/ml) in the visfatin level (p = 0.61). The difference in the visfatin level between patients with active and inactive manifestations did not reach statistical significance (6.13 ± 3.20 and 4.25 ± 2.73, respectively; p = 0.07). There was no significant difference according to the gender of the patients or the presence of clinical manifestations

Association of killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands with susceptibility to Behçet�s� disease

Objectives: Behçet�s disease (BD) is a systemic inflammatory disorder with remissions and exacerbations. It is thought that defects in the natural killer (NK) cell repertoire may be involved in BD through killer cell immunoglobulin-like receptors (KIRs). This study aimed to evaluate KIR and HLA genes, their interactions in BD patients, and their associations with clinical manifestations. Method: The presence or absence of KIR and HLA alleles and genotypes was analysed by polymerase chain reaction sequence-specific primer on genomic DNA of 397 BD patients and 300 healthy controls. Results: None of the KIR genes showed significant effects on BD susceptibility. HLA-C1Asn80 showed a protective effect against BD, whereas HLA-C2Lys80, HLA-B-Bw4Ile80, HLA-B5, and HLA-B51 were associated with a susceptibility risk for BD. In the combination of KIR and HLA genes, the frequencies of HLA genotypes no. 2, 3, 5, and 8, and inhibitory KIR no. 4 were significantly higher in patients than in controls. The frequencies of KIR genotype no. 3 and HLA genotypes no. 1, 4, 6, 7, and 9 were significantly lower in patients than in controls. There were many associations between KIR and HLA genes with clinical features of BD. Conclusion: Differences in the frequency of HLA genes, KIR�HLA interactions, and genotypes between BD and healthy controls and their associations with clinical manifestations indicate that NK cells are involved in BD pathogenesis. The observed differences indicated an NK cell activity imbalance in BD patients, and suggest a role of the KIR-HLA repertoire in the development of BD. © 2018 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation

Association of killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands with susceptibility to Behçet�s� disease

Objectives: Behçet�s disease (BD) is a systemic inflammatory disorder with remissions and exacerbations. It is thought that defects in the natural killer (NK) cell repertoire may be involved in BD through killer cell immunoglobulin-like receptors (KIRs). This study aimed to evaluate KIR and HLA genes, their interactions in BD patients, and their associations with clinical manifestations. Method: The presence or absence of KIR and HLA alleles and genotypes was analysed by polymerase chain reaction sequence-specific primer on genomic DNA of 397 BD patients and 300 healthy controls. Results: None of the KIR genes showed significant effects on BD susceptibility. HLA-C1Asn80 showed a protective effect against BD, whereas HLA-C2Lys80, HLA-B-Bw4Ile80, HLA-B5, and HLA-B51 were associated with a susceptibility risk for BD. In the combination of KIR and HLA genes, the frequencies of HLA genotypes no. 2, 3, 5, and 8, and inhibitory KIR no. 4 were significantly higher in patients than in controls. The frequencies of KIR genotype no. 3 and HLA genotypes no. 1, 4, 6, 7, and 9 were significantly lower in patients than in controls. There were many associations between KIR and HLA genes with clinical features of BD. Conclusion: Differences in the frequency of HLA genes, KIR�HLA interactions, and genotypes between BD and healthy controls and their associations with clinical manifestations indicate that NK cells are involved in BD pathogenesis. The observed differences indicated an NK cell activity imbalance in BD patients, and suggest a role of the KIR-HLA repertoire in the development of BD. © 2018 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation

Association of killer cell immunoglobulin-like receptor (<i>KIR</i>) genes and their <i>HLA</i> ligands with susceptibility to Behçet’s‎ disease

<p><b>Objectives</b>: Behçet’s disease (BD) is a systemic inflammatory disorder with remissions and exacerbations. It is thought that defects in the natural killer (NK) cell repertoire may be involved in BD through killer cell immunoglobulin-like receptors (KIRs). This study aimed to evaluate <i>KIR</i> and <i>HLA</i> genes, their interactions in BD patients, and their associations with clinical manifestations.</p> <p><b>Method</b>: The presence or absence of <i>KIR</i> and <i>HLA</i> alleles and genotypes was analysed by polymerase chain reaction sequence-specific primer on genomic DNA of 397 BD patients and 300 healthy controls.</p> <p><b>Results</b>: None of the <i>KIR</i> genes showed significant effects on BD susceptibility. <i>HLA-C1^Asn80</i> showed a protective effect against BD, whereas <i>HLA-C2^Lys80, HLA-B-Bw4^Ile80, HLA-B5</i>, and <i>HLA-B51</i> were associated with a susceptibility risk for BD. In the combination of <i>KIR</i> and <i>HLA</i> genes, the frequencies of HLA genotypes no. 2, 3, 5, and 8, and inhibitory KIR no. 4 were significantly higher in patients than in controls. The frequencies of KIR genotype no. 3 and HLA genotypes no. 1, 4, 6, 7, and 9 were significantly lower in patients than in controls. There were many associations between <i>KIR</i> and <i>HLA</i> genes with clinical features of BD.</p> <p><b>Conclusion</b>: Differences in the frequency of <i>HLA</i> genes, KIR–HLA interactions, and genotypes between BD and healthy controls and their associations with clinical manifestations indicate that NK cells are involved in BD pathogenesis. The observed differences indicated an NK cell activity imbalance in BD patients, and suggest a role of the KIR-HLA repertoire in the development of BD.</p