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Background/aim: In children with autosomal dominant polycystic kidney disease (ADPKD), clinical manifestations range from severe neonatal presentation to renal cysts found by chance. We aimed to evaluate demographic, clinical, laboratory findings, and genetic analysis of children with ADPKD. Materials and methods: We evaluated children diagnosed with ADPKD between January 2006 and January 2019. The diagnosis was established by family history, ultrasound findings, and/or genetic analysis. The demographic, clinical, and laboratory findings were evaluated retrospectively. Patients < 10 years and >= 10 years at the time of diagnosis were divided into 2 groups and parameters were compared between the groups. Results: There were 41 children (M/F: 18/23) diagnosed with ADPKD. The mean age at diagnosis was 7.2 +/- 5.1 (0.6-16.9) years and the follow-up duration was 59.34 perpendicular to 40.56 (8-198) months. Five patients (12%) were diagnosed as very early onset ADPKD. All patients had a positive family history. Genetic analysis was performed in 29 patients (PKD1 mutations in 21, PKD2 mutations in 1, no mutation in 3). Cysts were bilateral in 35 (85%) of the patients. Only one patient had hepatic cysts. No valvular defect was defined in 12 patients detected. Only 1 patient had hypertension. None of them had chronic kidney disease. No difference could be demonstrated in sex, laterality of the cysts, maximum cyst diameter, cyst or kidney enlargement, follow-up duration, or GFR at last visit between Groups 1 and 2. Conclusion: The majority of children with ADPKD had preserved renal functions and slight cyst enlargement during their follow-up. However, they may have different renal problems deserving closed follow-up.

Interleukin-1β (IL-1β), which is secreted by host tissues leading to periodontal tissue inflammation, is a major pro-inflammatory cytokine in the pathogenesis of periodontal disease. The conversion of pro-IL-1β into its biologically active form is controlled by multiprotein complexes named as inflammasomes, which are key regulator of host defense mechanisms and inflammasome involved diseases, including the periodontal diseases. Inflammasomes are regulated by different proteins and processes, including pyrin domain (PYD)-only proteins (POPs), CARD-only proteins (COPs), tripartite motif family proteins (TRIMs), autophagy, and interferons. A review of in vitro, in vivo, and clinical data from these publications revealed that several inflammasomes including (NOD)-like receptor (NLR) pyrin domain-containing 3 (NLRP3) and absent in melanoma 2 (AIM2) have been found to be involved in periodontal disease pathogenesis. To the best of our knowledge, the current article provides the first review of the literature focusing on studies that evaluated both inflammasomes and their regulators in periodontal disease. An upregulation for inflammasomes and a downregulation of inflammasome regulator proteins including POPs, COPs, and TRIMs have been reported in periodontal disease. Although interferons (types I and II) and autophagy have been found to be involved in periodontal disease, their possible role in inflammasome activation has not evaluated yet. Modulating the excessive inflammatory response by the use of inflammasome regulators may have potential in the management of periodontal disease.

WOS: 000463722800005, PubMed ID: 31365342, Objective: Familial Mediterranean fever (FMF) is the most common inherited monogenic autoinflammatory disease worldwide. It is caused by loss-of-function mutations in the MEFV gene, mostly affecting Eastern Mediterranean population. It is discussed if it should be considered an autosomal-dominant disease with variable penetrance, because heterozygosis mutations are associated with clinical autoinflammatory manifestations. Colchicine constitutes that the mainstay of FMF treatment should be preventing acute attacks and amyloidosis, and decreasing the chronic inflammation. In colchicine-resistant or intolerant patients, recent insights into the pathogenesis of FMF have made the anti-IL1 treatments important. We aimed to search for the retrospective results of canakinumab treatment in patients with FMF who are unresponsive to colchicine. Methods: In this study, 22 (13 males and nine females) patients with FMF with colchicine resistance/intolerance, age ranging from 6 to 18 years, were included in Ege University Department of Pediatric Rheumatology. After clinical and genetic diagnosis, colchicine treatment with standard doses was started. After treatment with canakinumab, complete response to treatment was determined as no acute episodes and normal level of acute phase reactants. Results: After canakinumab treatment, 22 patients with FMF who were colchicine-resistant were evaluated. After the treatment, no attack was observed in 19 patients, and the values of acute phase reactants were normal in 22 patients. In three patients, disease attack was observed 16 months after the first dose treatment. In all patients, the values of acute phase reactants were found at normal level during treatment. No drug-related side effects were observed in any patient. Conclusion: Canakinumab is an effective and safe anti-IL1 agent to reduce attacks in patients with FMF with no response to colchicine and to reduce the level of high-level laboratory findings associated with FMF.

[No abstract available]

OBJECTIVE RET/PTC in FNA (Fine needle aspiration) biopsy smears could improve the FNA diagnosis. The aim of study determining the prevalence of RET/PTC mutation in cases where thyroid nodules in ATA USG according to risk catogory is determined and investigating the relation of malignancy. METHODS RNA was extracted from 60 routine FNA. RET/PTC rearrangements were detected by real-time quantitative polymerase chain reaction, and, in parallel, RT-PCR is used to detect the chimeric RET/PTC1, RET/PTC2 and RET/PTC3 transcripts in RNA extracted from FNA. RESULTS A total of 75% FNA RET rearrangements were detected in the 20 PTC patients. RET/PTC positive was detected in 35% of cases without cancer (sensitivity 75%, specificity 65%) (p = 0,003). Significant correlation was found between A-high suspicion USG group (80%), B- intermediate suspicion USG group (45%) and C- low suspicion USG group (20%) in of RET/PTC rearrangements (p = 0.001). A significant correlation was found between the USG groups and the PTC (respectively group A,B,C: 60%, 30%, 10%)(p = 0.003). There was a statistical difference related to in the USG groups frequency between Classic type PTC (70%) and Follicular type PTC (30%)(p = 0.019). There was a statistical difference related to between RET/PTC and PTC types in the USG groups (p = 0.012). There was a statistical difference related to between usg groups tumor diameter A and C (P = 0.010). CONCLUSİON Molecular testing of FNA samples improves presurgical diagnosis. RET/PTC was found to be significantly higher in the diagnoses of the PTC with 75% sensitivity and 65% specificity

[No Abstract Available]

Uveitis is a chronic inflammatory disease. Chronic inflammation has been shown to have a role in pathogenesis of atherosclerosis. Atherosclerosis is the most important risk factor of cardiovascular diseases and is shown to start as early as childhood. In this study, we investigated the presence of subclinical atherosclerosis in children with uveitis. Seventy five patients who were diagnosed as having uveitis in ophthalmology and pediatric rheumatology clinics were included in the study. Patients with hypertension, obesity, dyslipidemia, diabetes, and with history of early cardiovascular disease were excluded. Arterial stiffness, carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), and carotid artery intima-media thickness (cIMT) were measured for each patient. These measurements were compared with 50 healthy children with similar age and sex as controls. The mean age of patients in this study was 12.24 ± 2.69 years, and the mean age of controls was 11.32 ± 4.52 years. PWV and AIx values were higher in the patient group (p = 0.04, p = 0.03). cIMT levels were not different in patient and control groups. When patients were grouped as having uveitis for more than 5 years or not, patients with longer duration of uveitis had higher PWV, AIx, and cIMT levels (p values were 0.01, 0.02, and 0.04 respectively). Vascular functions deteriorate first with endothelial damage in children with uveitis and as disease continues, increase in cIMT is added. We think that for follow-up of the disease and evaluation of the treatment, non-invasive subclinical atherosclerosis markers should be used along with activation criteria of primary diseases.

Mutations in the Methyl-CpG-binding protein 2 (MECP2) gene have been implicated in the etiology of Rett syndrome (RTT), a neurodevelopmental disorder that primarily affects girls. MECP2 mutations in males, once thought to be lethal, are now recognized with a broad spectrum of clinical manifestations. Here we report a 3-year-old boy who presented with developmental problems and regression and eventually was diagnosed with RTT that genetic analysis revealed to be a hemizygous c.316C>T missense mutation in the MECP2 gene suggesting somatic mosaicism with the normal 46,XY karyotype. DNA analysis of the patient’s mother showed this either to be a de novo mutation or a case of gonadal mosaicism. To the best of our knowledge, this is the first case report of RTT in a young boy with a hemizygous c.316C>T mutation in the MECP2 gene.

Background the inflammasome modulates the release of key proinflammatory cytokines associated with periodontal disease pathogenesis. the aim of this study was to evaluate the expression of proteins that regulate the inflammasome, namely pyrin domain-only proteins (POPs), caspase activation recruitment domain (CARD)-only proteins, and tripartite motif-containing (TRIM) proteins, in periodontal diseases. Methods A total of 68 participants (34 males and 34 females) were divided into four groups, including periodontal health (H), gingivitis (G), chronic periodontitis (CP), and aggressive periodontitis (AgP) based on clinical parameters. Gingival tissue samples were obtained from all participants for reverse transcription polymerase chain reaction (RT-PCR)-based gene expression analyses of molecules that regulate the inflammasome, including apoptosis-associated speck-like protein (ASC) containing CARD, caspase-1, interleukin-1 beta (IL-1 beta), interleukin-18 (IL-18), nucleotide-binding domain, leucine rich family (NLR) pyrin domain containing 3 (NLRP3), NLR family pyrin domain containing 2 (NLRP2), AIM2 (absent in melanoma 2), POP1, POP2, CARD16, CARD18, TRIM16, and TRIM20 by RT-PCR. Results NLRP3 and IL-1 beta were upregulated in the G, CP, and AgP groups compared with group H (P < 0.05). AIM2 was downregulated in the CP group compared with the H, G, and AgP groups (P < 0.05). TRIM20, TRIM16, and CARD18 were downregulated in the G, CP, and AgP groups compared with the H group (P < 0.05). POP1 and POP2 were downregulated in the CP and AgP, and AgP and G groups, respectively (P < 0.05). Conclusion Active periodontal disease may result in downregulation of inflammasome regulators that may increase the activity of NLRP3 and IL-1 beta in periodontal disease., Scientific and Technological Research Council of Turkey (TUBITAK), Ankara, TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK), This study was not supported by any financial organization. the corresponding author of this study (Kubra Aral) was supported with a scholarship by the Scientific and Technological Research Council of Turkey (TUBITAK), Ankara, Turkey. the authors report no conflicts of interest related to this study.

Amaç: Mezenkimal kök hücreler (MKH) güçlüimmünomodülatör hücreleridir ve ayrıca tümör mikroçevresinin bir bileşenidir.Bu çalışmada meme tümör hücre hatları MDA-MB-231 ve MCF-7’nin immün evazifmoleküller olan Indoleamine 2,3-dioxygenase (IDO), Human Leukocyte Antigen G(HLA-G) and Programmed Death-Ligand 1 (PD-L1) ifadelerine yağ dokusu kökenlimezenkimal kök hücrelerin etkilerini araştırmayı amaçladık. Yöntemler: Bu amaçla MKH, MDA-MB-231 ve MCF-7hücrelerini artan dozlarda interferon gama (IFN-g) ile kültüre edildi. Başkabir kültür kabında MKH’ler ile tümör hücreleri trans-well insertler ve aynıIFN-g uyarımı ile kültür edildi. Kültür süresinin bitiminde HLA-G ve PD-L1ifadeleri flow-sitmotetri yöntemi ile IDO ifadeleri Luminex yöntemi ile analizedildi. Bulgular: Düşük dozlu IFN-g uyarımında (10 ng/mL),MSC'lerin MCF-7 hücrelerinin HLA-G ve PD-L1 ekspresyonunda önemli bir artışayol açtığını bulduk. Aksine, yüksek doz IFN-g ile (50 ng/mL) bu ifadelerin heriki tümör hücresinde de önemli ölçüde azaldığını gördük. Ek olarak, MDA-MB-231hücrelerinin IDO ekspresyonunun MSC'lerin varlığında anlamlı şekilde arttığını,ancak MCF-7 hücrelerinin etkilenmediği gördük. Sonuç: Sonuç olarak, MDA-MB-231 hücreleri içinMSC'ler, sitotoksik hücrelerin baskılanmasında ve T hücrelerinin tükenmesindeönemli bir rol oynayan HLA-G ve PD-L1 ekspresyonunu azalttığı için koruyucu birrol oynayabilir. Öte yandan, MSC'ler yüksek IDO seviyeleri için önemli birkaynak olabilir ve bu nedenle anti-tümör immün yanıtı olumsuz yönde etkileyebilir.Bununla birlikte, verilerimiz diğer çalışmalarla desteklenmelidir., Aim:Mesenchymal stem cells (MSCs) are strong immunomodulatory cells and a componentof the tumor microenvironment. In this study, we aimed to investigate theeffects of MSCs derived from adipose tissue on the expressions of immuneevasive molecules indoleamine 2,3-dioxygenase (IDO), human leukocyte antigen G(HLA-G) and programmed death-ligand 1 (PD-L1) of breast tumor cell linesMDA-MB-231 and MCF-7. Methods:For this purpose, MSCs, MDA-MB-231 and MCF-7 cells were cultured with increaseddoses of interferon gamma (IFN-g). In another plate, tumor cells were culturedin transwell inserts using the same IFN-g stimulation to evaluate the effect ofMSCs. At the end of the culture period, the HLA-G and PD-L1 expression wasdetected by flow cytometry, and IDO expression by the Luminex method. Results:We found that in low-dose IFN-g stimulation (10 ng/mL), MSCs led to asignificant increase in the HLA-G and PD-L1 expression of MCF-7 cells. On thecontrary, at a high dose of IFN-g (50 ng/mL), their expression significantlydecreased in both tumor cells. In addition, we observed that the IDO expressionof MDA-MB-231 cells was significantly increased in the presence of MSCs, butMCF-7 cells were not affected. Conclusion:In conclusion, for MDA-MB-231 cells, MSCs may play a protective role because theyreduce the expression of HLA-G and PD-L1 that are involved in the suppressionof cytotoxic cells and exhaustion of T cells. On the other hand, MSCs may be animportant source of high IDO levels, and therefore may negatively affect theantitumor immune response. However, our data should be supported by furtherstudies.

WOS: 000471326300002, Background: Infantile nephrotic syndrome (INS) refers to disease that is present after the first three months of life up to one year of age. There is genetic heterogeneity and genotype-phenotype correlation is not clear. Objectives: The focus of the present study was to analyze genotypic and phenotypic features of both NPHS1 and NPHS2 genes in INS. Methods: Clinical data, mutational analysis, histology, treatments, and outcomes of 48 children with NS are evaluated. A direct sequencing of NPHS1 gene and NPHS2 gene was performed. Patients were classified into 3 groups; group 1: cases having only NPHS1 mutation; group 2: cases with only NPHS2 mutation; group 3: cases without any mutation. Results: The mean age at onset of the disease was 8.7 +/- 2.3 months, and mean follow-up time was 8.3 years. Seven familial and 41 sporadic cases of INS were found. Kidney biopsy was performed in 45 out of 48 patients and pathological investigations revealed focal segmental glomerulosclerosis in 29 (65%), IgM nephropathy in 6 (13%), and minimal change disease in 10 patients (22%). There were 5 (10.4%) cases in groups (patients having only mutations of NPHS1)and 13 cases (27%) in group 2 (patients having only mutations of NPHS2). Thirty cases (62.5%) had neither NPHS1 nor NPHS2 mutation (group 3). Conclusions: The genotypic and phenotypic features of INS were demonstrated. We found that INS with podocin mutation has poor prognosis according to exonal distribution. NPHS1 mutations caused a severe disease but with a more favorable prognosis.

WOS: 000463332100016, PubMed ID: 30968627, Brugada syndrome, an arrhythmogenic disease, occurs due to mutations involving cardiac sodium channels. It is characterized by persistent or transient ST-segment elevation in the right precordial electrocardiogram leads that could be unmasked by several circumstances, with fever particularly. Molecular and cellular mechanisms leading to Brugada syndrome have not been completely elucidated. Mutations of the SCN5A gene encoding the pore-forming alpha-subunit of the cardiac sodium channel protein have been attributed in the molecular diagnosis. Although this syndrome is well-known in adults, it is less frequently reported in infants and children. We describe a 9-year-old Turkish boy with a family history of sudden cardiac death, who presented with chest pain and fever-induced expression of the Brugada syndrome phenotype that might be associated with a mutation in SCN5A gene.

WOS: 000399263300015, PubMed ID: 28367892, The effects of bodybuilding and protein supplements on periodontal tissues have not yet been evaluated. The present study aimed to examine the periodontal status and interleukin (IL)-1 beta, apoptosis-associated speck-like protein containing C-terminal caspase-recruitment domain (ASC), and caspase 1 (CASP1) gene expression levels of body builders compared with those of controls. Twentyfive bodybuilders with gingivitis (BB-G) who used protein powder supplements were compared with 25 nonexercising males with (G) and 25 without (H) gingivitis. Saliva, gingival crevicular fluid (GCF), and serum were collected for gene expression analysis. Plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were recorded. GI and BOP were higher in group BB-G and G than in group H (P < 0.01), but PI, PD, and CAL were similar between groups (P > 0.05). In GCF, CASP1, ASC, and IL-1 beta expression were upregulated in group G compared with groups BB-G and H (P < 0.01). In addition, ASC (P < 0.05) and IL-1 beta (P < 0.01) were downregulated in group BB-G compared with group H. CASP1, IL-1 beta (P < 0.01), and ASC in the saliva were downregulated in group BB-G compared with groups H and G (P < 0.05). CASP1, IL-1 beta, and ASC may play a role in the pathogenesis of gingivitis. Bodybuilding and supplement usage may decrease gingival inflammation by downregulating CASP1, and ASC., Scientific Research Fund of Sifa University [SUBAP 2015-6], This study was supported by the Scientific Research Fund of Sifa University, Project Grant # SUBAP 2015-6.

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.

WOS: 000388033500006, PubMed ID: 27357501, Nucleotide binding and oligomerization domains/caspase recruitment domain-containing protein 15 (NOD2/CARD15) is a cytoplasmic molecule controlling apoptosis and inflammatory processes by recognizing some microbial components. We aimed to identify the frequencies of NOD2/CARD15 gene mutations in patients with gouty arthritis and to determine their possible correlation with the disease phenotype. The study included 93 patients with gouty arthritis and 51 healthy controls matched for age, gender, and ethnicity. The NOD2/CARD15 R702W and G908R gene mutations were explored by the polymerase chain reaction restriction fragment length polymorphism method while the 3020insC mutation was analyzed by DNA sequencing. The mean patient age was 54.2 +/- 14.2 years and mean duration of the disease was 3.1 +/- 2.9 years. The first metatarsophalangeal and finger joint involvements were detected in 72 (77.4%) and 18 (19.5%) patients, respectively. Ankle arthritis and knee arthritis were detected in 43 (46.2%) and 20 (21.5%) patients, respectively. In total, 4 (9%) heterozygous mutations were detected in the G908R and R702W genes, while no mutation was detected in the 3020insC gene. Compared to the control group, there were no significant differences in all three DNA regions (G908R, R702W, and 3020insC; p = 0.452, p = 0.583, and p = 0.350, respectively). No correlation between the NOD2/CARD15 variants and clinical or laboratory findings (p > 0.05) was found. The frequencies of the NOD2/CARD15 gene mutations in the patients were similar to healthy control group. No association between clinical or laboratory findings and the NOD2/CARD15 gene mutations was observed., scientific research project committee of Sifa University, This work was supported by the scientific research project committee of Sifa University.

Gouty arthritis is a chronic erosive autoinflammatory disease. Pyrin has anti-inflammatory effects in the regulation of inflammasome and is encoded by the MEFV gene. The relationship between different rheumatic diseases and the MEFV gene mutations was demonstrated. The aim of this study was to determine the frequency of MEFV gene mutations in patients with gouty arthritis and identify a possible correlation with disease phenotype. Ninety-three patients with gouty arthritis and 102 healthy controls, compatible with age, gender and ethnicity, were included in the study. MEFV gene mutations were investigated by PCR method. Out of 93 patients with gouty arthritis, 36 (38.7 %) showed MEFV gene mutations carriage, whereas 20.6 % in healthy control group. Distribution of mutations identified in patients with gouty arthritis was as; R202Q in 18 (19.3 %), E148Q in 5 (5.4 %), K695R in 4 (4.3 %), M680I in 2 (2.1 %), V726A in 2 (2.1 %), P369S in 2 (2.1 %), R408Q in 2 (2.1 %), M694 V in 1 (1.1 %), respectively. Three patients were identified with compound heterozygosity. Distribution of MEFV gene mutations carriage in healthy controls was; E148Q in 11 (10.7 %), M694 V in 2 (1.9 %), M694I in 1 (0.9 %), M680I in 2 (1.9 %), V726A in 1 (0.9 %), A744S in 1 (0.9 %), K695R in 2 (1.9 %), and P369S in 1 (0.9 %) patients, respectively. Higher MEFV gene mutations carrier frequency was observed in patients with gouty arthritis, compared with the control group (p = 0.009). Heterozygous R202Q was the most common mutation detected in patients with gouty arthritis, while heterozygous E148Q in healthy control group. Statistically significant difference was not detected between clinical findings of gouty arthritis and the MEFV gene mutations (p > 0.05). We determined higher prevalence of MEFV gene mutations in patients with gouty arthritis compared with the healthy control group. The most frequently detected mutation was heterozygous R202Q, whereas E148Q in healthy controls. High carriage rates of MEFV gene mutations in gouty arthritis suggest that it may play an important role in the pathogenesis of the disease and predisposition to the disease.

WOS: 000395365500020, PubMed ID: 28261298, Introduction: Chronic myeloproliferative disorders (CMPD) are chronic myeloid hematological disorders, characterized by increased myeloid cell proliferation and fibrosis. Impaired apoptotic mechanisms, increased cell proliferation, uncontrolled hematopoietic cell proliferation and myeloaccumulation may contribute to the pathogenesis of CMPD. The aim of our study was to show the possible role of FAS/FASL gene polymorphisms in CMPD pathogenesis and investigate the association with clinical parameters and susceptibility to disease. Material and methods: We included 101 (34 polycythemia vera (PV), 23 primary myelofibrosis (PMF), 44 essential thrombocythemia (ET)) CMPD patients diagnosed according to the WHO classification criteria and 95 healthy controls in this study. All the patients and the controls were investigated for FAS/FASL gene expression, allele frequencies and phenotype features, and also FAS mRNA levels were analyzed. Results: Chronic myeloproliferative disorders patients showed increased FAS-670AG + GG genotype distribution compared with the control group (p < 0.05). While the A allele was more frequent in both groups, AG genotype was more frequent in CMPD patients. There was no association between FAS-670A>G gene polymorphism and some clinical parameters such as splenomegaly and thrombosis (p > 0.05). No statistically significant difference in FASL+843C>T genotype or allele frequency was found between groups (p > 0.05). Moreover, no statistically significant difference was detected in FASL and JAK2V617F mutations (p > 0.05). FAS mRNA expression was 1.5-fold reduced in patients compared to healthy subjects. Conclusions: According to our findings, FAS/FASL gene expression may contribute to the molecular and immunological pathogenesis of CMPD. More investigations are needed to support these data.

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.

WOS: 000459055600002, PubMed ID: 30793612, OBJECTIVES: The aim of the study was to determine the mutation of the podocin gene (NPHS2) in children with minimal changes diseases (steroid sensitive nephrotic syndrome (NS)) and steroid resistant NS. BACKGROUND: Despite the fact that the role of genetic factors is a well-known phenomenon, in NS there are still unknown aspects that are yet to be discovered. NS, type 2 is caused by NPHS2 gene and is characterised with proteinuria, minimal change disease on renal biopsy, poor response to steroid treatment, etc. METHODS: Twenty-nine children (65.5 % male, 34.5 % female) with nephrotic syndrome caused by chronic glomerulonephritis were examined and patients were tested for NPHS2 gene with Sanger technique. RESULTS: The average age was 7.2 +/- 2.65 years. 82.8 % of patients had NS with minimal changes, 17.2 % had a steroid resistant NS. The analysis of the NPHS2 gene revealed a likely pathogenic (Arg168His), uncertain significance (Pro20Ley, Leu169Pro, Val180Met, Arg229Gln, Val290Met) and benign (Gly34Gly, Ala318Ala) variants. No novel variants were detected. CONCLUSION: This is the first study investigating the nephrotic syndrome related to NPHS2 gene in Azerbaijani population. The high prevalence of uncertain significance variants emphasises the importance of population studies in this region as such data are necessary for classifications of the detected genetic variants (Tab. 1, Ref. 25). Text in PDF www.elis.sk.

WOS: 000469770400004, PubMed ID: 31144657, Background/Aims: Gastric cancers vary across countries and ethnic groups. They are the second most common type of cancer worldwide. Dietary and non-dietary factors as well as genetic and epigenetic alterations of many mechanisms are implicated in the development of gastric cancer. We aimed to determine the sequence of possible nucleotide changes, polymorphisms, and mutations, and to establish genotype and phenotype relation by performing whole DNA sequence analysis of the XRCC1 and ERCC1 genes belonging to base excision repair (BER) and nucleotide excision repair (NER) family of DNA repair genes in patients with gastric cancer. Materials and Methods: We included 50 patients of both sexes who had received diagnosis of gastric cancer and 50 healthy people who showed same demographic traits that forms the control group. We analyzed the ERCC1 and XRCC1 genes by DNA sequence analysis on both groups. After the analysis, we compared the genotype-phenotype relation. Results: Neither patients nor the control group has any nucleotide replacement in any exon of ERCC1 genes. We could not detect significant difference between patients and healthy groups when we correlated genotype contribution of mutations Arg194Trp, Arg208His, Arg399Gln detected in the XRCC1 gene and allele frequency. Conclusion: According to our study, the ERCC1 gene in Turkish population is not getting mutation in patients with gastric cancer and healthy individuals. Three mutations were detected in the XRCC1 gene, and these mutations were not associated with gastric cancer.

Hermle, Tobias/0000-0002-0441-7749, WOS: 000508269600010, PubMed: 31732614, Background Mutations in about 50 genes have been identified as monogenic causes of nephrotic syndrome, a frequent cause of CKD. These genes delineated the pathogenetic pathways and rendered significant insight into podocyte biology. Methods We used whole-exome sequencing to identify novel monogenic causes of steroid-resistant nephrotic syndrome (SRNS). We analyzed the functional significance of an SRNS-associated gene in vitro and in podocyte-like Drosophila nephrocytes. Results We identified hemizygous missense mutations in the gene TBC1D8B in five families with nephrotic syndrome. Coimmunoprecipitation assays indicated interactions between TBC1D8B and active forms of RAB11. Silencing TBC1D8B in HEK293T cells increased basal autophagy and exocytosis, two cellular functions that are independently regulated by RAB11. This suggests that TBC1D8B plays a regulatory role by inhibiting endogenous RAB11. Coimmunoprecipitation assays showed TBC1D8B also interacts with the slit diaphragm protein nephrin, and colocalizes with it in immortalized cell lines. Overexpressed murine Tbc1d8b with patient-derived mutations had lower affinity for endogenous RAB11 and nephrin compared with wild-type Tbc1d8b protein. Knockdown of Tbc1d8b in Drosophila impaired function of the podocyte-like nephrocytes, and caused mistrafficking of Sns, the Drosophila ortholog of nephrin. Expression of Rab11 RNAi in nephrocytes entailed defective delivery of slit diaphragm protein to the membrane, whereas RAB11 overexpression revealed a partial phenotypic overlap to Tbc1d8b loss of function. Conclusions Novel mutations in TBC1D8B are monogenic causes of SRNS. This gene inhibits RAB11. Our findings suggest that RAB11-dependent vesicular nephrin trafficking plays a role in the pathogenesis of nephrotic syndrome., Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [HE 7456/3-1]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK076683, U54HG006504]; MOTI-VATE program of the Medical Faculty of theUniversity of Freiburg; National Human Genome Research InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [UM1HG008900]; National Eye InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI); National Heart, Lung, and Blood InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI); T32 Ruth L. Kirschstein Institutional National Research Service AwardUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK007527]; Charite-Universitatsmedizin Berlin; Berlin Institute of Health; German Research FoundationGerman Research Foundation (DFG) [RO4341/2-1]; Excellence Initiative of the German Research FoundationGerman Research Foundation (DFG) [EXC 294]; Ministry of Science, Research and the Arts of Baden-Wurttemberg [Az: 33-7532.20]; Deutsche Forschungsgemeinschaft Collaborative Research CentreGerman Research Foundation (DFG) [KIDGEM1140]; Federal Ministry of Education and ResearchFederal Ministry of Education & Research (BMBF) [01GM1515C]; NATIONAL HUMAN GENOME RESEARCH INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [UM1HG008900, UM1HG008900, UM1HG008900, UM1HG008900, UM1HG008900] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [T32DK007527, T32DK007527, T32DK007527, T32DK007527, T32DK007527] Funding Source: NIH RePORTER, This research was supported by grants from the Deutsche Forschungsgemeinschaft to Dr. Hermle (HE 7456/3-1) and the National Institutes of Health to Dr. Hildebrandt (DK076683), and to the Yale Center for Mendelian Genomics (U54HG006504). Ms. Kampf was supported by the MOTI-VATE program of the Medical Faculty of theUniversity of Freiburg. the Broad CMG was funded by a grant from the National Human Genome Research Institute (UM1HG008900), the National Eye Institute, and the National Heart, Lung, and Blood Institute. A. Onuchic-Whitford acknowledges support from the T32 Ruth L. Kirschstein Institutional National Research Service Award (DK007527). Dr. Schrezenmeier is participant in the BIH-Charite Clinician Scientist Program funded by the Charite-Universitatsmedizin Berlin and the Berlin Institute of Health. Dr. Romer acknowledges the support by the German Research Foundation (grant RO4341/2-1), the Excellence Initiative of the German Research Foundation (EXC 294), and the Ministry of Science, Research and the Arts of Baden-Wurttemberg (Az: 33-7532.20). Dr. Bergmann acknowledges support from the Deutsche Forschungsgemeinschaft Collaborative Research Centre (KIDGEM1140) and the Federal Ministry of Education and Research (01GM1515C).

WOS: 000438380400011, PubMed ID: 29745120, Complement mediated hemolytic uremic syndrome which is caused by excessive activation of the alternative complement system is a thrombotic microangiopathy. The disease frequently occurs as a result of mutations in the genes that regulates complement proteins. Complement factor H gene has the most common mutations. A nine-month-old male patient was transferred to pediatric intensive care unit with the diagnosis of hemolytic uremic syndrome. Nonsense heterozygous p.Arg1215X mutation in the complement factor H gene was detected. The patient who had pulmonary, intestinal and hepatic involvement accompanying acute renal failure was successfully treated with therapeutic plasma exchange and eculizumab. Nonsense heterozygous p.Arg1215X mutation is extremely rare and can cause severe hemolytic uremic syndrome. As far as we know, our patient is the third case with this mutation in the literature.

Background: Severe combined immunodeficiency (SCID) syndromes are a heterogenous group of diseases characterized by impairment in both cellular and humoral immunity with a range of genetic disorders. Complete recombinase activating gene (RAG) deficiency is associated with classical T - B - NK + SCID which is the most common phenotype of Turkish SCID patients. There is a broad spectrum of hypomorfic RAG mutations including Omenn syndrome, leaky or atypical SCID with expansion of γδ T cells, autoimmunity and cytomegalovirus (CMV) infections. Methods: Twenty-one (44%) patients had RAG1 deficiency of all 44 SCID patients followed up by pediatric immunology department. A retrospective analysis was conducted on the medical records of all SCID patients with RAG1 deficiency. Results: Eight patients were classified as T - B - NK + SCID, five patients as T + B - NK + SCID (three of these were Omenn phenotype), and eight patients as T + B + NK + SCID phenotype. Mean age of the whole study group, mean age at onset of symptoms and mean age at diagnosis were 87.7 ± 73.8 (12 - 256), 4.4 ± 8.2 (1 - 36) and 29.1 ± 56.8 (1 - 244) months, respectively. Consanguinity was present in 11 (52%) of 21 patients. Autoimmunity was found in six patients (28%). Ten patients (47%) had CMV infection, four (19%) had Epstein-Barr virus (EBV) infections and three (14%) had Bacillus Calmette-Guerin (BCG) infections. Seven patients who had refractory cytopenia (two pancytopenia and five bicytopenia) underwent bone marrow biopsy, three of whom had bone marrow fibrosis. Future evaluations must be considered about bone marrow fibrosis in RAG1 deficiency patients. Eosinophilia was observed in 10 patients, seven of whom did not have Omenn phenotype. Conclusion: Non-Omenn phenotype RAG1 deficiencies can also present with eosinophilia. This report is presented to emphasize that RAG1 mutations may lead to diverse clinical phenotypes. J Clin Med Res. 2016;8(5):379-384 doi: http://dx.doi.org/10.14740/jocmr2316w

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.

WOS: 000219054200003, Aim: Glycogen storage disease type 1 is characterized with hypertriglyceridemia which does not lead to atherosclerosis. The human intercellular adhesion molecule-1 gene has been shown to be affected in atherosclerosis and postprandial hypertriglyceridemia. Materials and Methods: In the present paper, the authors genotyped the Glu241Arg polymorphism in the intercellular adhesion molecule-1 gene in 35 patients with Glycogen storage disease type 1 and 108 healthy controls. Results: The results indicated a significant decrease in the frequency of the GG genotype in Glycogen storage disease type I patients compared to healthy controls. In addition, a significant correlation between the GG genotype and triglyceride levels was seen in Glycogen storage disease type 1 patients. Conclusion: It is thus concluded that the GG genotype could protect Glycogen storage disease type I patients from the development of atherosclerosis.

WOS: 000443041100012, Arthrogryposis, renal tubular dysfunction and cholestasis (ARC) syndrome is a rare, autosomal recessive multisystem disorder. Severe growth retardation, ichthyosis, recurrent febrile disease, platelet abnormalities, sensorineural hearing loss, hypotonia and corpus callosum dysgenesis were later included as further features of this syndrome. We present a case of ARC syndrome diagnosed by genetic analysis.

BACKGROUND The aim of the study was to investigate the effects of colchicine on cytokine production, apoptosis, alveolar bone loss, and oxidative stress in an experimental model of periodontitis in rats. METHODS Forty-eight rats were divided equally into four groups: healthy (H); periodontitis (P); periodontitis+colchicine low dose (CL, 30 μg/kg/day), and periodontitis+colchicine high dose (CH, 100 μg/kg/day). After 11 days, interleukin (IL) -1β, IL-8, and IL-10 were analyzed in gingival samples using Enzyme-Linked ImmunoSorbent Assay. Receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), total oxidative stress (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured in gingiva and serum. Alveolar bone volume was evaluated via micro-CT. Apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in histological sections. RESULTS Colchicine treatment significantly reduced IL-1β, IL-8, RANKL, RANKL/OPG, TOS, OSI, and bone volume ratio levels, and increased TAS levels compared to group P (p

The aim of the present study is to investigate matrix metalloproteinase (MMP)-8 and tissue inhibitor of MMP-1 (TIMP-1) gene polymorphisms in generalized aggressive periodontitis (GAgP) and to assess the effects of MMP-8 and TIMP-1 genotypes on the outcomes of non-surgical periodontal therapy.Genomic DNA was obtained from peripheral blood of 100 patients with GAgP and 167 periodontally healthy controls. MMP-8 +17 C/G, -799 C/T, -381 A/G and TIMP-1 372 T/C, *429 T/G polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. Patients with GAgP received non-surgical periodontal therapy and were followed for 6 months. Clinical periodontal parameters and gingival crevicular fluid (GCF) samples were collected at baseline and at follow-up visits. GCF biomarkers were analyzed by immunofluorescence assay and enzyme-linked immunosorbent assay.Distribution of the MMP-8 -799 C/T genotypes was significantly different between the GAgP and control groups (P0.005). TIMP-1 372 T/C and *429 T/G genotypes in males were also significantly different between study groups (P0.004). GCF MMP-8 levels decreased until 3 months after non-surgical therapy compared with baseline in T and G alleles, as well as G and C allele carriers (P0.0125), whereas no significant decreased was observed in non-carriers (P0.0125).On the basis of the present findings, it can be suggested that MMP-8 -799 C/T and TIMP-1 372 T/C, *429 T/G gene polymorphisms in males may be associated with the susceptibility to GAgP in the Turkish population.

The researchers investigated the relationship between intense training, the catechol-Omethyltransferase (COMT) Val108/158Met gene polymorphism, and alexithymia. Eighteen female and 77 male athletes...

Hiperimmünglobülin D sendromu mevolinat kinaz genindeki mutasyonların neden olduğu otozomal resesif geçişli nadir görülen otoinflamatuvar bir hastalıktır. Hastalık klinik olarak infantil dönemde tekrarlayan ateş atakları ile karakterizedir. Ateşe tipik olarak karın ağrısı, kusma, ishal ve servikal lenfadenopati bazen de deri ve eklem semptomları eşlik eder. Bu olgu sunumunda 12 aylıktan itibaren tekrarlayan ateş, halsizlik, aftöz ülserler, servikal lenfadenopati, alt ekstremitelerde maküler döküntüler, şiddetli kas ağrıları, karın ağrısı ve hepatosplenomegalinin eşlik ettiği ataklar ile prezente olan 6 yaşında bir erkek hasta sunulmuştur. Hastanın atakları sırasında eritrosit sedimentasyon hızı, C-reaktif protein ve fibrinojen düzeyleri yüksek seyrediyordu. Serum IgD düzeyi ise hem atak sırasında hem de atak dışında yüksek seyrediyordu. Mevalonat kinaz gen analizinde heterozigot Ser52Asn mutasyonu saptandı. Literatürde bu mutasyonun klinik bulgu göstermediği bildirilmektedir. Profilaktik kolşisin ve intravenöz immünglobülin tedavisine yanıt vermeyen hastamız, aynı zamanda ataklar sırasında kullanılan non-steroid antiinflamatuvar ilaçlar ve kortikosteroid tedavisinden de fayda görmedi. Hastanın ateş atakları anti interlökin-1 tedavisinden sonra azaldı., Hyperimmunoglobulinemia D syndrome is a rare, autosomal recessively inherited autoinflammatory disease caused by mutations in the mevalonate kinase gene. The disease is characterized by clinically recurrent episodes of fever in the infantile period. The fever is typically accompanied by abdominal pain, vomiting, diarrhea and cervical lymphadenopathy, and sometimes by skin and joint symptoms. In this case report, a 6-year-old male patient who was presented with a history of attacks of recurrent fever, malaise, aphthous ulcers, cervical lymphadenopathy, macular rash in the lower extremity, severe muscle pain, abdominal pain and hepatosplenomegaly since the age of 12 months is presented. During the attacks, the erythrocyte sedimentation rate, C-reactive protein and fibrinogen levels of the patient were elevated. The serum IgD level was high both during and outside the attack. Mevalonate kinase gene analysis revealed the heterozygote Ser52Asn mutation. In the literature, it is reported that this mutation does not show clinical signs. The patient did not respond to prophylactic colchicine and intravenous immunoglobulin treatment, and also to non-steroidal anti-inflammatory drugs and corticosteroids during the attacks. The patient's fever attacks decreased with anti-interleukin-1 treatment.

PubMed ID: 29058690, Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney disease. Here, we identified recessive mutations in the gene encoding the actin-binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL mutations resulted in a marked loss of its actin-bundling ability, truncation of AVIL also disrupted colocalization with F-actin, thereby leading to impaired actin binding and severing. Additionally, AVIL colocalized and interacted with the phospholipase enzyme PLCE1 and with the ARP2/3 actin-modulating complex. Knockdown of AVIL in human podocytes reduced actin stress fibers at the cell periphery, prevented recruitment of PLCE1 to the ARP3-rich lamellipodia, blocked EGF-induced generation of diacylglycerol (DAG) by PLCE1, and attenuated the podocyte migration rate (PMR). These effects were reversed by overexpression of WT AVIL but not by overexpression of any of the 3 patient-derived AVIL mutants. The PMR was increased by overexpression of WT Avil or PLCE1, or by EGF stimulation; however, this increased PMR was ameliorated by inhibition of the ARP2/3 complex, indicating that ARP-dependent lamellipodia formation occurs downstream of AVIL and PLCE1 function. Together, these results delineate a comprehensive pathogenic axis of SRNS that integrates loss of AVIL function with alterations in the action of PLCE1, an established SRNS protein., VE 196/1-1, HE 7456/1-1, Jo 1324/1-1 U.S. Public Health Service: DK-56338 National Institutes of Health: DK076683 National Institute of Diabetes and Digestive and Kidney Diseases: DK-98120 National Research Foundation of Korea, NRF: 2015R1D1A1A01056685 Department of Science and Technology, Government of Kerala NAS LPDS-2015-07 Fudan University, We are grateful to the families and study participants for their contributions. We thank the Yale Center for Mendelian Genomics (U54HG006504) for WES analysis. FH is a William E. Harmon Professor of Pediatrics. This research was supported by the NIH (DK076683, to FH); the Young Scholars Program of Children’s Hospital of Fudan University (to JR); Basic Science Research Program through the National Research Foundation of Korea 2015R1D1A1A01056685 (to HYG); DFG fellowships (VE 196/1-1, to ATvdV; Jo 1324/1-1, to TJS; and HE 7456/1-1, to TH); the German National Academy of Sciences Leopoldina (LPDS-2015-07, to EW); the Egyptian Group for Orphan Renal Diseases (EGORD) (to NAS); the Department of Science and Technology, Government of India (DST-SERB, to MAJ); the National Institute of Diabetes and Digestive and Kidney Diseases (DK-98120, to SK); and the Public Health Service (DK-56338, to SK).

Aim: Metabolic syndrome (MetS) is a major risk factor for both diabetes mellitus and cardiovascular disease (CVD). The aims of the study were 1) to investigate the insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) gene polymorphisms in patients with MetS and 2) to examine the relationships between gene polymorphisms and components of MetS. Patients & Methods: The study population included 100 patients with MetS and 30 patients without MetS as control group. Metabolic syndrome (MS) was defined as in ATP III. Entire coding exons of IRS-1 and IRS-2 genes were amplified by polymerase chain reaction (PCR). Insulin resistance (IR) was estimated using the homeostasis model assessment (HOMA). Results: In patients with MetS, 34 (34%), had G972R (rs1801278) gene polymorphism and 66 (66%) had no nucleotide substitutions at the IRS-1 gene (p circumference, blood pressure, triglyceride, HDL-Cholesterol, LDL-Cholesterol and HOMA-IR levels. Conclusion: Insulin receptor substrate-1 and 2 gene polymorphisms were associated with metabolic syndrome but not its components.

We aims investigate Turkish type 2 diabetic patients with/without diabetic foot ulcers and healthy group and examined the contribution of Interleukin (IL)-6 -174 GC gene polymorphism to the development of diabetic foot ulcers.The Interleukin (IL)-6 -174 GC genotypes were determined prospectively in 50 patients with diabetic foot ulcers and 35 without diabetic foot ulcers and a control group of 119 healthy individuals. Genotyping of the Interleukin (IL)-6 -174 GC gene polymorphisms for all individuals was performed by PCR-RFLP method.The genotype IL6 distribution did differ between the control group (CC 13.3%, GC 66.7%, GG 20%) and type 2 diabetic patients (CC 2.4%, GC 47.1%, GG 50.6%) (P0.001). The genotype IL6 distribution did not differ between type 2 diabetic patients group (CC 0%, GC 45.7%, GG 54.3%) and diabetic foot ulcers (CC 4%, GC 48%, 48%) (P0.05). The frequency of the polymorphic G allele in between the control group and type 2 diabetic patients was no similar for the groups (58.4% and 74.1%, respectively) (p0.05). The frequency of the polymorphic G allele in between the type 2 diabetic patients and diabetic foot ulcers was similar for the groups (77.1% and 72%, respectively) (p0.05).The gene polymorphism of Interleukin-6 -174 GC and G allele are an risk factor for diabetes, but gene polymorphism of Interleukin-6 -174 GC is not an independent risk factor for diabetic foot. Genetic factors in the pathogenesis of diabetic foot may also show any changes in different populations.

Sarcoidosis is a chronic granulomatous disease. Pyrin has anti-inflammatory activity in the regulation of inflammasomes and is encoded by the Mediterranean fever (MEFV) gene. MEFV gene mutations trigger the inflammatory cascade and cause familial Mediterranean fever (FMF). A relationship between various rheumatic diseases and MEFV gene mutations has been demonstrated. The aim of this study was to determine the prevalence of the MEFV gene mutation in Turkish patients with sarcoidosis and to detect any possible correlation with disease phenotype.The study included 78 sarcoidosis patients and 85 healthy subjects matched for age, gender, and ethnicity. MEFV gene mutations were investigated with the FMF strip assay, which is based on reverse hybridization of biotinylated polymerase chain reaction (PCR) products.Of the 78 patients with sarcoidosis, nine (11.5%) were found to be carriers of MEFV gene mutations. The distribution of these nine mutations were: three (3.8%) V726A, two (2.5%) E148Q, two (2.5%) M680I, one (1.3%) A744S, and one (1.3%) K695R. Carriers of M694V, M694I, R761H, and P369S were not detected in any of the sarcoidosis patients. None of the sarcoidosis patients were found to be compound heterozygous carriers. The prevalence of the MEFV gene mutation carrier detected in the healthy control group was 22.4%. The distribution of the 19 MEFV gene mutations found in the healthy controls was: nine (10.6%) E148Q, two (2.3%) M694V, one (1.2%) M694I, one (1.2%) M680I, two (2.3%) V726A, one (1.2%) A744S, two (2.3%) K695R, and one (1.2%) P369S. When compared with the control group, a lower prevalence of the MEFV gene mutation carrier was found in sarcoidosis patients but this was not statistically significant (p = 0.067). In nine patients found to be MEFV gene mutation carriers, higher serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels and higher numbers patients with arthritis, enthesitis, and ankle arthritis were found (p = 0.01, p = 0.04, p = 0.028, p = 0.05, p = 0.05, respectively).When we compared Turkish sarcoidosis patients with the healthy control group, we found a lower prevalence of MEFV gene mutations. In sarcoidosis patients, the MEFV gene mutation carrier was found to be related to high acute-phase responses, arthritis, and enthesitis. The existence of MEFV gene mutations may have a preventive role with regard to the development of sarcoidosis. Prospective studies that include larger patient populations are needed.

Retinitis pigmentosa (RP) is an inherited progressive retinal disease with a complex inheritance pattern affecting about 1 in 3,500 people worldwide. To date, a large number of sequence changes in the causal contributor genes of wide-spectrum heterogeneous RP were reported, including deletions, insertions, or substitutions that lead missense mutations or truncations. Here we present an association between the clinical presentations of adRP and sequence variants involving novel M216L mutation in the RHO gene together with nonsynonimous sequence changes R872H, N985Y, A1670T, S1691P, C2033Y, and synonimous Q1725Q with novel, N1521N, and T1733T SNPs in the RP1 gene of uncertain pathogenicity in a Turkish family with autosomal dominant retinitis pigmentosa.

Interleukin (IL)-10 is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. IL-10 has met the criteria for an anti-inflammatory and an immunosuppressive cytokine, its activity may be important for clinical outcome of diabetic nephropathy (DN). We aimed at evaluating the relation between the genotypic and allelic frequencies of the IL-10 (-1082G/A) polymorphisms, and their association with the risk to develop DN in the Turkish population.The (IL)-10 (-1082G/A) genotypes were retrospectively determined in 43 patients with nephropathy and 48 without nephropathy and a control group of 112 healthy individuals. The polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism.This genotype distribution was different between control subjects and patients with type 2 diabetes in which 24.2% were AA, 75.8% were GA, and 0% were GG (p0.001). The frequency of the mutant G allele was 36.1% in patients with diabetes nephropathy versus 39.6% in those without nephropathy (p0.05). The genotype frequencies were AA, 27.9%; GA, 72.1%; and GG, 0% in patients with diabetes with nephropathy versus AA, 20.8%; GA, 79.2%; and GG, 0% in those without nephropathy (p0.05).The polymorphisms of IL-10 (-1082G/A) genes were significantly associated with the occurrence of patients with type 2 diabetes. The IL-10 (-1082G/A) genotype and allele frequencies were not different between patients with diabetes with nephropathy and those without nephropathy. Therefore, we conclude that the IL-10 (-1082G/A) gene polymorphism is not associated with the development of DN in Turkish patients with type 2 diabetes.

Congenital nephrotic syndrome (CNS) is a rare disease inherited as an autosomally recessive trait and defined as proteinuria manifesting at birth or in the first 3 months of life. The classical form is the Finnish type of CNS (CNF), which is caused by mutations in the nephrin gene (NPHS1). The classical findings include prematurity, large placenta and massive proteinuria. Minor cardiac findings have been reported as a minor functional disorder but CNS with major cardiac malformation is rare. Here we report the case of a Turkish child with CNS with small indel mutation (c.614_621delCACCCCGGinsTT) in exon 6 of NPHS1 and also major cardiac malformation who did not develop end-stage renal disease until the age of 5 years.

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder characterized by episodes of inflammation in the absence of high-titer autoantibodies or antigen-specific T cells. The Mediterranean fever (MEFV) gene located on chromosome 16p13.3, which encodes the 781-amino-acid protein pyrin, is the causative gene for this monogenic Mendelian disease. This study presents the molecular analysis of an MEFV gene mutation screen of 5518 Turkish individuals with clinical diagnoses of FMF. Patients were genetically diagnosed using the FMF StripAssay and DNA sequencing analysis. Contrary to the results achieved by the FMF StripAssay, DNA sequencing analysis identified large-scale coding and noncoding novel sequence variants, together with a significant group (76%) of individuals who were receiving colchicine and had a single heterozygous mutation, despite the recessive inheritance of FMF. In conclusion, sequence analysis, unlike other routine laboratory techniques, may enable screening for a broad range of nucleotide variations and may prevent less common, population-restricted, novel sequence variants from being overlooked.

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.

To evaluate genetic variations of innate immune system such as mannose binding lectin (MBL), Toll like receptor 4 (TLR4), CD14, LY96 (MD2) and Uroplakin 1B (UPK1B) genes in children with recurrent urinary tract infection (UTI).The study included 30 children with recurrent UTI and 30 healthy controls. Blood was drawn and analysed for genetic polymorphisms of MBL, TLR4 and CD14 genes by the PCR-RFLP method. Direct DNA sequencing analysis was performed for LY96 and UPK 1B gene mutation in 10 children from UTI group and 5 children from control group.TLR4 gene Thr399Ile polymorphism was not observed in any child. Genotype distribution and allele frequency of Asp299Gly polymorphism was similar in both groups (p = 0.55). Codon 54 polymorphism of the MBL gene was similar in UTI and control groups (p = 0.49). -159 CC/CT/TT genotypes of CD14 gene was similar between the two groups (p = 0.14). UPK1B and LY96 gene DNA sequence analysis was similar in UTI and control groups.This study is the first study in which different parts of the innate immune system were evaluated in UTI etiopathogenesis in Turkish children. The results did not point out a significant role of any of the genes evaluated in this study.