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Familial Mediterranean Fever (FMF, OMIM ID: 249100) is the most common autoinflammatory, autosomal recessive disease caused by mutations in the MEFV gene. It is widespread in the Mediterranean, primarily among Turkish, Armenian, Arab and Jewish. This study aims to examine genotype distributions of common MEFV variants in the Turkish population using targeted NGS and to evaluate all rare mutations. It included 3230 people applying to Ege University Children's Hospital Molecular Medicine Laboratory with the suspicion of auto inflammatory disease between 2017 and 2021. MEFV missense variant was detected in 1839 (56.9%) individuals. One or more mutations were found in them. 1063 patients were heterozygous (57.8%), 410 were compound heterozygous (22.3%), 238 were complex genotype (12.9%), and 128 were homozygous (7%). 56 different mutations and 141 genotypes were detected, two of which were novel (p.His87Arg, c.260A > G and p.Leu396Phe, c.1186C > T). These were determined as 6benign, 40 uncertain significant, 3 likely pathogenic and 7 pathogenic according to the ACMG classification. The most common ones were R202Q (n = 1097, 37.48%), E148Q (n = 512, 17.49%), M694V (n = 493, 16.84%), V726A (n = 155, 5.30%), M680I (n = 150, 5.12%), P369S (n = 108, 3.69%), R408Q (n = 95, 3.25%) respectively. They constitute 89.17 % of the entire patient population. In conclusion, DNA variants/mutations in the MEFV gene were evaluated in 3230 patients. To date, no mutation screening has been encountered in such a large population using NGS. Genotype distributions of both common and rare mutations were revealed. The obtained data will hopefully contribute to the future genotype phenotype studies of FMF disease.

15-lipoxygenase (15-LOX) is a critical enzyme that allows the direction of arachidonic acid metabolism to change from inflammation into the resolution. This study aims to reveal how the immunomodulation properties of mesenchymal stem cells (MSC) alter by the 15-LOX overexpression. For this purpose, peripheral blood mononuclear cells (PBMCs) isolated from seven healthy volunteers, and both MSCs and 15-LOX overexpressing MSCs (15-LOXMSCs) were co-cultured at different cell ratios (1/1, 1/5 and 1/10). Alterations of CD4+Tbet+, CD4+Gata3+, CD4+RoRC2+, and CD4+FoxP3+ lymphocyte frequencies were detected by flow cytometry, and IFN-?, IL-4, IL-6, IL-10, IL-17a, TGF-? and LXA4 levels of medium supernatants were measured by ELISA method. According to our findings, MSC and 15-LOXMSCs have a suppressive effect on PHA activated PBMCs. However, as the ratio of PBMCs increased, the effects of 15-LOXMSCs increased significantly, while the effects of MSCs decreased. The most notable effect of the 15-LOX modification was the significant reduction in IL-6, IL-10 and IL-17a expression and the accompanying increase in TGF-? and LXA4 levels. We also observed a similar situation between CD4+RoRC2+ and CD4+FoxP3+ cell frequencies. These data suggested that the effects of MSCs on the balance of Th17 / Treg could change by the 15-LOX overexpression, and this might be in favor of the Treg cells. © 2021, 16-TIP-041, The Scientific Research Projects Commission of Ege University financially supported the project for this study, with the reference number 16-TIP-041 .

Introduction Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy, which develops as a result of defective activity of the alternative complement pathway and excessive complement activation due to genetic or acquired factors. No satisfactory responses were obtained by plasmapheresis, corticosteroids and fresh frozen plasma (FFP) transfusion. However, promising results are obtained in recent years by eculuzimab treatment, which inhibits C5 activation. Objective To evaluate the efficacy, safety and effect of eculizumab on quality of life of adult aHUS patients followed in our center. Materials and Methods Seven patients who received eculizumab treatment in single center between the years 2012 and 2016 due to aHUS diagnosis were retrospectively evaluated. Patients were diagnosed with aHUS in accordance with certain criteria, after eliminating all the other factors caused by thrombotic microangiopathy. Complement gene mutations were completed in six patients. All patients received eculizumab as recommended (900 mg/per two weeks) following plasmapheresis, FFP, corticosteroid and hemodialysis (HD) treatments. Results Four out of seven patients were men and three were women; average patient age was 51.1 (26–69) years and average duration of disease was 25.3 (2–45) months. Average period from the initial complaints of the patients up to aHUS diagnosis was 4.2 (2–13) months. Tests were implemented on six patients for complement gene mutations, and complement factor H (CFH) homozygous mutation was identified in three patients. Complete remission was observed in four patients and partial remission in two patients after eculizumab; however, one patient died. Plasmapheresis was discontinued in patients with complete remission, whereas two patients with partial remission continued the HD program, despite normalization in hematologic parameters. Significant improvement was observed in post-treatment quality of life in all six patients who currently continue eculuzimab treatment. No transfusion reaction and/or no serious infections were observed in any of the patients, while URTI (upper respiratory tract infection) was observed in one patient. Discussion Eculizumab is an effective and safety treatment option in adult aHUS patients. Early diagnosis and initializing eculizumab therapy at an early stage may decrease mortality and morbidity in patients with aHUS. New studies are required on this topic.

Hashimoto's disease is a polygenic disorder with complex etiopathogenesis. The imbalance between pro- and anti-inflammatory cytokines may play a role in the etiology. We aimed to evaluate the relation between 174 promoter region of the interleukin 6 rs1800795 gene polymorphism in patients with Hashimoto's thyroiditis (HT). We studied 110 HT patients and 110 healthy controls. The evaluation of genotype for interleukin 6 rs1800795 gene polymorphism were performed by using PCR-RFLP method. The genotype of IL6 distribution did differ between the control group (CC 17.3%, GC 78.2%, GG 4.5%) and the HT patients (CC 29.1%, GC 46.4%, GG 24.5%) (p 0.05). Our results indicate that interleukin 6 rs1800795 polymorphism may be associated with susceptibility to HT in Turkish Patients. It is necessary to confirm the results and determine the underlying pathogenic mechanisms in further studies.

Introduction Several studies have attempted to define the diagnostic criteria of the geriatric syndrome sarcopenia. Studies of sarcopenia prevalence in Turkey are limited; one reason for this is the absence of standard diagnostic reference values. The aim of this study was to investigate the prevalence of sarcopenia and its influencing factors in the local elderly nursing home residents in accordance with the EWGSOP consensus report. Materials and methods The study included a total of 211 nursing home residents. Anthropometric measurements, muscle mass, muscle strength and physical performance were examined. Muscle mass of the nursing home residents was compared to an 18–45-year-old healthy control group. Descriptive values for numerical variables are given as mean, standard deviation; categorical variables are shown as frequency and percentage. Results A total of 211 nursing home residents were included in the study. The average age was 77.30 ± 7.20; the participants were 58.8% women and 37.4% young-old. The prevalence of sarcopenia in Turkish nursing home residents was found to be 33.6%. Among sarcopenic participants, 32.4% were women and 67.6% were men. In our study, sarcopenia was more prevalent in men, the young-old, and patients with Parkinson's or chronic obstructive lung disease, while sarcopenia was seen less in obese patients. No relationship was found between the Barthel index and sarcopenia. Conclusions Sarcopenia prevalence was 33.6% when the diagnostic criteria described by the EWGSOP were used. Sarcopenia prevalence was higher in men and the young-old age groups. Sarcopenia was more frequent in nursing home residents with malnutrition or risk of malnutrition.

Objective Recent studies have showed that genetic factors involved in the host responses might determine the severity of periodontitis. hCAP-18/LL-37 is a part of the innate immune response in the oral cavity. The aim of the present study was to investigate the mutation of CAMP gene encoding hCAP-18/LL-37 in the patients with different periodontal diseases. Design Seventy-eight chronic periodontitis, 72 generalized aggressive periodontitis, and 149 controls were analysed for mutation of CAMP gene using direct DNA sequencing method. Frequencies of p.S34N mutation were compared by Pearson chi-square test. Logistic regression analysis was used to analyse the association between periodontitis and p.S34N mutation adjusting for bleeding on probing, age and gender. Results Twenty-five subjects had a novel missense mutation of CAMP gene. Single base substitution (c.101G>A) in exon 1 led to p.S34N mutation. All amino acid substitutions were heterozygous mutation. The patients with generalized aggressive periodontitis had significantly higher p.S34N mutation prevalence compared to the others, whilst there was no significant difference in prevalence of p.S34N mutation between the patients with chronic periodontitis and the control subjects. Logistic regression analysis adjusted for BOP, age and gender revealed that the patients with generalized aggressive periodontitis were 5.32 times more likely to have p.S34N mutation compared to the controls (OR = 5.32, 95% CI: 1.3–22.1). Conclusion We report a novel missense mutation of CAMP gene. p.S34N mutation in CAMP gene seems to be contributing factor for generalized aggressive periodontitis, but not for chronic periodontitis.

Toll-like receptor (TLR) gene polymorphism is known to impair intracellular signaling pathways following adaptive immune responses. Our aim was to investigate the distribution of TLR4 and TLR2 gene polymorphisms among pediatric renal transplantation patients in relation to chronic allograft nephropathy (CAN). In addition to 115 healthy controls, we included 69 renal recipients, 19 of whom were identified as CAN by biopsy scored according to the Banff criteria. Polymorphisms at TLR4 Asp299Gly and/or Thr399Ile were present in 11.6% of renal transplant recipients. None of these subjects was identified in cosegregation with the Thr399Ile allele, whereas three had an isolated Asp299Gly and five had an isolated Thr399Ile. Neither renal recipients nor healthy controls were homozygous for both Asp299Gly and Thr399Ile polymorphisms. However, TLR4 Thr399Ile polymorphism and Ile allele was greater among CAN (-) versus CAN (+) recipients (P.05). The frequency of TLR2 mutant type Gln allele was significantly higher in recipients than among healthy controls (P.0001). However, the Gln allele frequency was similar between CAN (+) and CAN (-) patients. The results of present study may be speculated to show TLR4 and TLR2 gene polymorphisms as protective factors from CAN development due to impaired immune responses.

Host response to periodontopathic microorganisms can be modulated by genetic factors. Accumulated evidence highlighted the role of renin-angiotensin system (RAS) in inflammatory response thus potential implication of this molecular system in the pathogenesis of periodontitis can be suggested. The present study investigated common genetic variants of molecules within the RAS family namely angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) in relation to generalized aggressive periodontitis (G-AgP).DNA was obtained from peripheral blood of 103 G-AgP patients and 100 periodontally healthy subjects. ACE I/D, AGT M235T and AT1R A1166C polymorphisms were genotyped by polymerase chain reaction and restriction fragment length polymorphism method. Chi-square, ANOVA and logistic regression were used in statistical analyses.Both ACE I/D and AT1R polymorphisms were similar in G-AgP and healthy groups (p0.05). G-AgP subjects exhibited decreased AGT TT genotype and T allele frequency as compared to healthy subjects (p0.05). The same trend was also observed in the nonsmoker subgroup regarding investigated RAS polymorphisms.Present findings suggest that AGT M235T TT genotype and T allele might be associated with decreased risk for G-AgP in Turkish population.

Background: Non-alcoholic fatty liver disease (NAFLD) is common in obese and diabetics. Serine protease inhibitor Kazal-1 (SPINK-1) protein is highly expressed in the liver and adipose tissue of diabetic and obese suggesting its role in NAFLD. SPINK-1 also behaves as an acute phase reactant protein. Some genetic factors including the genetic variations in SPINK-1 protein have been linked to chronic pancreatitis and diabetes. We therefore hypothesized that SPINK-1 mutations might be a risk factor for the development of NAFLD. Methods: Liver biopsy proven fifty NAFLD cases (20 steatohepatitis, 30 diffuse fatty liver disease and 44 healthy controls were included to the study. Liver function tests were measured. Body mass index was calculated. Insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Common genetic mutations in the third exon of SPINK-1 gene were analyzed by direct sequencing method. Results: We found two cases with a SNP at N34S location in NAFLD group (allele frequency %4). One subject with diffuse fatty liver disease and other with liver cirrhosis due to NAFLD had N34S mutation. No SNPs were detected in healthy controls. In conclusions, in limited number of patients SPINK-1 mutations were not considered as a risk factor alone for NAFLD development.

Aim Matrix metalloproteinases (MMPs) are involved in periodontal tissue remodeling and degradation. MMP polymorphisms could alter transcription and function of these enzymes. The aim of this study was to investigate MMP-2 , MMP-9 and MMP-12 gene polymorphisms in relation to susceptibility to severe chronic periodontitis (CP). Methods Genomic DNA was obtained from peripheral blood of 87 severe CP patients and 107 periodontally healthy subjects. MMP-2 − 735C / T , MMP-9 − 1562C / T and MMP − 12 357Asn / Ser gene polymorphisms were genotyped by polymerase chain reaction and restriction fragment length polymorphism. Probing depth, clinical attachment loss, supragingival plaque accumulation and bleeding on probing were recorded. The data were analyzed by chi-square, logistic regression and Mann–Whitney- U -tests. Results The genotype distributions and allele frequencies of MMP-2 , MMP-9 and MMP-12 genes were similar in CP and healthy subjects ( p > 0.05). Differences between rare allele carriage rates of CP and healthy groups regarding MMP-2 , MMP-9 and MMP-12 gene polymorphisms were not significant ( p > 0.05). However, T allele carriers of MMP-9 − 1562 gene had less risk for CP (OR = 0.36; 95% CI = 0.16–0.81). Conclusion These data suggest that MMP-2 − 735C / T , MMP-9 − 1562C / T and MMP-12 357Asn / Ser polymorphisms are not associated with susceptibility to severe CP in Turkish population. However, T allele of MMP-9 − 1562 gene might be associated with decreased susceptibility to severe CP.

Transforming growth factor-beta(1) (TGF-beta(1)) has significant effects on periodontal host response regulation. Limited knowledge on the role of TGF-beta(1) in various periodontal disease types and particularly in advanced periodontitis forms warranted the present study. The aim of the present study was to evaluate the gingival crevicular fluid (GCF) TGF-beta(1) levels in patients with different forms of periodontal disease.GCF TGF-beta(1) levels were investigated in 32 chronic periodontitis (CP), 30 generalized aggressive periodontitis (G-AgP), 15 gingivitis patients and 16 periodontally healthy subjects. Periodontal status was evaluated by measuring probing depth, clinical attachment loss, plaque and bleeding on probing. TGF-beta(1) levels were analyzed by enzyme-linked immunosorbent assay. The results were expressed in terms of total amount (pg) and concentration (pg/microl).G-AgP and CP groups had significantly elevated GCF TGF-beta(1) total amount compared to healthy group (p0.008). Moreover, GCF TGF-beta(1) total amount of G-AgP group was significantly higher than that of gingivitis group (p0.008). G-AgP and CP groups had similar GCF TGF-beta(1) total amount (p0.008). Significant correlation was found between GCF TGF-beta(1) total amount and all clinical periodontal parameters (p0.05).The results of the present study suggest contribution of TGF-beta(1) to the pathogenesis of advanced chronic and aggressive periodontitis. TGF-beta(1) may thus be one of the components modulating exaggerated host response together with other major mediators of inflammation.

Background: Genetic polymorphisms in the TGF-β1 gene were shown to interfere with the transcriptional activity of the TGF-β1 gene, and this influences the production, secretion or activity of the TGF-β1 growth factor. Transforming growth factor-β1 (TGF-β1) gene polymorphism is associated with risk of inflammatory diseases. Objectives: The aim of this study was to evaluate TGF-β1 gene polymorphisms in a Turkish population with different periodontal diseases and to investigate the association between TGF-β1 genotype and clinical periodontal parameters. Methods: A total of 134 subjects were included in this study. Genomic DNA was isolated from 51 patients with chronic periodontitis (CP), 43 with generalized aggressive periodontitis (G-AgP) and 40 healthy controls. Three TGF-β1 gene polymorphisms were identified by PCR-RFLP and MS-PCR at positions + 915G/C, Thr263Ile and 713/8delC. Probing pocket depth (PPD), clinical attachment loss (CAL), plaque accumulation (plaque %) and bleeding of probing were obtained. Chi-square, Mann–Whitney U test and logistic regression analysis were used. Results: There was a slightly significant difference in + 915C positive genotype distributions between CP and control groups (OR: 2.46, CI: 1.010–6.005, p = 0.047). No significant differences were present between G-AgP and controls in + 915C positive genotype. Thr263Ile and − 713/8delC genotype distributions were not different between study groups. There were significant differences in PPD and CAL scores between + 915C positive and negative CP patients. Conclusion: These findings suggest that the TGF-β1 (+ 915C) polymorphic allele might be associated with chronic periodontitis in the Turkish population.

Objectives Interleukin-1 receptor antagonist (IL-1Ra) gene (IL-1RN) polymorphism is associated with disease susceptibility and activity in several inflammatory diseases. The aim of this study was to investigate IL-1RN genotype and its associations with different periodontal diseases in a group of Turkish subjects. Design and methods A total of 293 subjects were included in this study. Genomic DNA was obtained from the peripheral blood of 52 patients with generalized aggressive periodontitis (G-AgP), 51 with chronic periodontitis (CP) and 190 reference subjects. A variable number tandem repeat (VNTR) polymorphism in the second intron of the IL-1RN gene was detected by PCR-based methods. Probing pocket depth, clinical attachment loss, plaque accumulation and bleeding on probing (BOP) were recorded. The data were analyzed by the χ2 test, logistic regression and Mann–Whitney U test. Results There were significant differences among the groups in the distribution of IL-1RN genotypes (P = 0.0001) and allele frequencies (P = 0.0001). The frequency of IL-1RN2 allele 2 positivity was higher in the AgP and CP group than the reference group [odds ratio (OR) 6.654, 95% CI: 3.023–16.648; OR 10.327, 95% CI: 4.758–22.412, respectively]. The percentage of sites with BOP was significantly higher in IL-1RN2+ compared to IL-1RN2− CP patients (P = 0.022). Conclusion These results suggest that IL-1RN2 allele positivity is associated with periodontal disease in a Turkish population.

Meconium aspiration syndrome (MAS) frequently results in inactivation of surfactant, persistent pulmonary hypertension (PPHN) and respiratory failure among newborn infants. Inflammation and inflammatory mediators play an important role in MAS. Since alveolar macrophages are thought to be very important cells in the pathogenesis of various inflammatory diseases, we evaluated whether meconium could stimulate rat alveolar macrophages to generate platelet-activating factor (PAF) and tumor necrosis factor (TNF)-alpha in vitro. We also examined the response to A23187 (calcium ionophore), 1-0-Hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (synthetic PAF) and dexamethasone on meconium-induced release of PAF and TNF-alpha. PAF and TNF-alpha concentrations from supernatant fluid were measured after high-performance liquid chromatography purification by specific radioimmunoassay, and TNF-alpha concentrations were determined by using an enzyme-linked immunosorbent assay. Our results showed that alveolar macrophages exposed to meconium could enhance PAF and TNF-alpha production in a dose (0.1, 1, 5 and 10%, P

Objectives: To assess the impact of the human FcγRIIA and FcγRIIIB gene polymorphisms on the risk of rheumatic fever (RF). Designs and methods: FcγRIIA-R/H-131 and FcγRIIIB-NA1/NA2 genotypes were determined using polymerase chain reaction in 66 RF cases and 117 healthy controls in this case control study. Results: Compared with healthy controls, the RR genotype was enriched in the entire group of RF cases (odds ratio [OR] 4.98, 95% confidence interval [95% CI] 1.81–13.70). RF patients were more frequently HR heterozygotes rather than HH homozygotes (OR 3.09 vs. 0.11). The results of this study show that patients who have RF are more likely to have the RR and HR genotypes than control children. These probabilities show that RR is associated with the greatest risk for rheumatic fever and HR is associated with an intermediate risk. For the distribution of FcγRIIIB NA2 genotypes, a nonsignificant increase was found in RF patients (39.31% vs. 51.51%; OR 1.64, P = 0.1226). Conclusion: The FcγRIIA-R/H-131 polymorphism may be an important marker in determining predisposition to RF.