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Objectives: 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. Method: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background/aim: Familial Mediterranean fever (FMF) is diagnosed by fever episodes with sterile peritonitis, arthritis, pleurisy, and erysipelas-like erythema. The relationship between phenotype and genotype in FMF has not been adequately explained. The aim of this study was to characterize the phenotype and genotype correlation in FMF. Materials and methods: Clinical diagnosis of FMF was conducted according to the Tel Hashomer criteria. Pras scoring was used to determine clinical severity. FMF strip assay analysis was used, and the hotspot regions were observed with PCR amplification and automatic DNA sequence analysis method. Results: We showed commonly seen mutations (most frequently M694V) in a study group of 191 patients. The disease severity score of patients with M694V mutation was high on the Pras scoring system. Patients with M694V mutation needed high colchicine dosages to control disease activity. R202Q was the most commonly seen polymorphism in 70 patients. The coexpression of R314R single nucleotide polymorphism on third exon was shown in our study. Moreover, D102D, G138G, and A165A subhaplotypes and E474E, Q476Q, and D510D subhaplotypes were also shown. Conclusion: DNA sequence analysis should be a commonly used method for progress in the field of molecular genetics and for the better understanding of the FMF phenotype and genotype relationships in all populations. [ABSTRACT FROM AUTHOR]

Abstract: Alcoholism is a complex genetically influenced disorder which refers to alcohol abuse and alcohol dependence. There are controversial results on the role of gene polymorphisms in alcohol dependence in the literature. Differences in population groups and selective inclusion criteria for alcohol dependence may affect results. In this study, we investigated the role of ADH1B Arg48His (rs1229984) and, ADH1C Ile350Val (rs698) gene polymorphisms in Turkish population. 100 healthy volunteers and 75 patients who were admitted to Ege University Alcohol Dependence Unit enrolled in the study. We found significant increase both in ADH1B (Arg48His) polymorphism Arg allele and Arg/Arg genotype frequency in patients. No profound connection between alcohol dependence and ADH1C Ile350Val gene polymorphism was detected. Alcohol dependence is an important health problem that depends on many genetic and environmental factors but we think that it is possible to interpret genetic risk for developing early diagnostic methods and treatment strategies by comprehensive linkage and association studies. [Copyright &y& Elsevier]

Background. In steroid-resistant nephrotic syndrome (SRNS), a considerable number of patient progress to end-stage renal disease (ESRD), despite aggressive therapy. The latest advance in familial focal segmental glomerulosclerosis (FSGS) has been the discovery of a mutant form of canonical transient receptor potential channel 6 (TRPC6) leading to FSGS through unclear mechanisms. The aim of this study is to screen for TRPC6 mutations in familial and sporadic SRNS patients. Methods. Twenty-five children with SRNS originating from Turkey were included in this study. Nine patients had familial and 16 patients had sporadic SRNS. Mutation analysis was performed in all 13 coding exons of the TRPC6 gene with the direct DNA sequencing method. The control group consisted of 50 normal healthy children originating from Turkey. Results. No mutation was detected in nine children (four familial, five sporadic). A variant (L395A) in one patient, intronic nucleotide substitution (c.171 + 16 A>G and c.171 + 86 G>C) in six patients and previously described missense (A404V; rs36111323) and synonymous (N561N; rs12366144) aminoacid variants in nine patients were found. Among patients with intronic, missense and synonymous aminoacid variants, 5 patients had familial and 11 patients had sporadic SRNS. Their mean age at onset of proteinuria was 2.6 ± 1.7 years. Seven cases (three familial, four sporadic) progressed to ESRD with a mean time of 10.2 ± 2.9 years. Conclusions. In conclusion, analysis of TRPC6 gene mutations in FSGS will provide new insights into the pathogenesis of nephrotic syndrome. Previous works have emphasized that the patients with only hereditary familial FSGS carried a missense mutation in the TRPC6 gene. Our findings suggest that TRPC6 mutations may also have an important role in the pathogenesis of sporadic SRNS. [ABSTRACT FROM PUBLISHER]

Familial Mediterranean fever (FMF) is a disease characterized by recurrent, self-limiting fever and serositis and caused by altered pyrin due to mutated MEFV gene. The aim of this study was to investigate clinical manifestations and MEFV mutations among patients with FMF and healthy controls in the Aegean region of Turkey. This study included 308 patients and 164 healthy controls. Patients were divided into three groups according to Tel-Hashomer criteria; definitive, probable, and suspicious. Among the patients, 146 were women (47.4%) and 162 were men (52.6%). The mean age (±SD) of the patients at the diagnosis was 9.6 ± 3.95 (range 0.5-18). The mean age (±SD) at onset of the symptom was 6.2 ± 3.95 (range 1-18). Symptoms were seen earlier onset in definitive group than the suspicious group in our cohort (4.7 ± 3.9 years, 6.6 ± 3.9 years, respectively; P = 0.001). Clinical features were abdominal pain (83.1%), fever (55%), arthritis (17.1%), myalgia (4.5%), pleuritis (10%), and erysipelas-like erythema (7.7%). Fever, arthralgia, arthritis, chest pain, and amyloidosis were found statistically significant more in definitive group than suspicious group ( P < 0.001, P < 0.001, P < 0.001, P < 0.05, and P < 0.001, respectively). MEFV gene mutations were identified in 199 patients (64.6%). The most commonly encountered MEFV mutation among the patients was M694V homozygote (25%). M694V homozygous mutation was found most frequently in definitive FMF group than other groups (49, 9, 8.9%, respectively). To our knowledge that FMF should be suspected in the case of non-specific but recurrent attacks of serositis and high fever, and molecular analysis should be performed in order to make diagnosis of FMF. [ABSTRACT FROM AUTHOR]

Oral Diseases (2010) , 60-67 To investigate the levels of antimicrobial peptide hCAP-18/LL-37 protein and mRNA expression in gingival tissues with different periodontal disease. Ten patients with generalized aggressive periodontitis, 10 patients with chronic periodontitis, and 10 healthy controls were included in this study. Periodontal parameters including probing depth, clinical attachment level, plaque index, and papilla bleeding index were assessed in study subjects. hCAP-18/LL-37 mRNA analysis by RT-PCR and immunohistochemistry were performed in 19 samples provided enough RNA in terms of concentration and integrity. This study demonstrated that hCAP-18/LL-37 was a product of neutrophils. Tissue samples of chronic periodontitis patients had significantly higher immunostaining of hCAP-18/LL-37 on neutrophils infiltrating in both epithelium and connective tissue compared with controls. hCAP-18/LL-37 mRNA expression levels in tissue samples of chronic periodontitis patients seemed to be upregulated compared with controls. While two generalized aggressive periodontitis patients showed downregulated hCAP-18/LL-37 mRNA expression levels, one generalized aggressive periodontitis patient showed slightly increased hCAP-18/LL-37 mRNA level compared with controls. hCAP-18/LL-37 has an important role in innate response during periodontal inflammation. Local deficiency in hCAP-18/LL-37 might be a confounding effect in the pathogenesis of generalized aggressive periodontitis. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Surgery / Ulusal Cerrahi Dergisi is the property of Turkish Surgery Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Angiotensin converting enzyme (ACE) plays an essential role in the renin–angiotensin system. It converts angiotensin I to angiotensin II and inactivates bradykinin and tachykinins. Numerous studies have been published investigating associations of the ACE gene I/D polymorphism with various pathophysiological conditions. We examined the prevalence of the ACE I/D polymorphism in a sample of healthy volunteers from western Turkey, including 1063 healthy Turkish controls. Analysis of the ACE I/D gene polymorphisms by polymerase chain reaction found frequencies of 16.1% for the II genotype, 47.7% for the ID genotype, and 36.2% for the DD genotype. The allele frequency was 39.9% for the I alleles and 60.1% for the D allele. This study demonstrates that the allele and genotype frequency values for the Turkish population are similar to previously published frequencies for Caucasian populations. [ABSTRACT FROM AUTHOR]

Aim: Evidence suggests that the ultimate product of the renin–angiotensin system (RAS), angiotensin II, exerts inflammatory actions. The present study aimed to evaluate the inter-relation between gene polymorphisms of the RAS components; angiotensin converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type-I receptor (AT1R), and severe chronic periodontitis (CP). Material and Methods: DNA was obtained from peripheral blood of 90 CP patients and 126 periodontally healthy subjects, and the clinical parameters were recorded. ACE I/D, AGT M235T and AT1R A1166C polymorphisms were genotyped by the PCR–RFLP method. Chi-square,anova and logistic regression methods were used in statistical analyses. Results: The frequency of the ACE D allele was significantly lower in the CP group than the healthy group ( pcorr=0.015). CP subjects exhibited increased C allele carriage and C allele frequency of the AT1R gene ( pcorr=0.03 and pcorr=0.03, respectively). All clinical parameters of CP patients were found to be similar in variant allele-carrying and non-carrying subjects ( p>0.05). Conclusions: The present findings suggest that ACE I/D and AT1R polymorphisms might be associated with susceptibility to CP but not with disease severity. The D allele of ACE I/D might be associated with decreased, whereas the C variant of AT1R A1166C might be associated with an elevated risk for CP in Turkish population. [ABSTRACT FROM AUTHOR]

Copyright of Anatolian Journal of Cardiology / Anadolu Kardiyoloji Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Fc receptors (FcR) play an important role in immune regulation. This might be linked to the variability in immune response, therefore relating to the pathogenesis of atopic diseases. The aim of the present study was to evaluate the Fc γRIIIa gene polymorphism in Turkish children with asthma and allergic rhinitis. The study included 364 atopic children (184 bronchial asthma, 180 allergic rhinitis) and 234 healthy subjects as the control group, aged between 5 to 16 years. Patients were recruited from outpatient clinics of allergy and general pediatric care. Plasma IgE concentrations were measured by immunoassays and skin prick test was done in children with atopic diseases. The Fc γRIIIa gene polymorphism was determined using the polymerase chain reaction method. Distribution of V158V genotype was significantly different among patient groups compared to controls (for asthmatic children OR: 5.33, 95% CI: 2.80–10.23, p < 0.001; for allergic rhinitis OR: 3.25, 95% CI: 1.75–6.07, p = 0.001). Distribution of 158 V allele was significantly different among asthmatic children (OR: 2.20, 95% CI: 1.65–2.92, p < 0.001) and allergic rhinitis patients (OR: 1.77, 95% CI: 1.32–2.35, p < 0.001) compared to healthy controls. Our study shows that the V158V genotype in Fc γRIIIa gene polymorphism may be a genetic risk factor for the development of atopic diseases. [ABSTRACT FROM AUTHOR]

The podocin ( NPHS2) gene encodes podocin protein, which has an important role in glomerular ultrafiltration and controlling slit membrane permeability. The detection of an NPHS2 mutation affects the treatment plan for children with nephritic syndrome (NS). The frequency and spectrum of podocin mutations in the Turkish population have remained largely unknown. The aim of this study was to screen for podocin mutations in Turkish patients with steroid-resistant NS (SRNS) and to compare it with other published series. There were 295 children with SRNS, originating from Turkey, included in this study. Forty-one patients (13.8%) had familial NS and 254 patients (86.2%) had sporadic NS. Mutation analysis was performed in all eight exons of the NPHS2 gene with the direct DNA sequencing method. There were 53 different pathogenetic NPHS2 mutations detected, including 37 novel mutations. The mutation detection rate was 24.7% for all patients, 29.2% for familial, and 24% for sporadic SRNS. The most common mutated exon was exon 5 (52 allele). The presence of mutations in exon 4 was found to increase the risk of end-stage renal disease (ESRD). Among patients with mutations, the rates of renal failure and/or ESRD (26%) were significantly higher than in those without mutations (12.6%). The mean time of progression to renal failure and ESRD in patients with mutations (1.8 ± 2.5 years) was significantly shorter than in patients without mutations (3.7 ± 4.0 years). Additionally, in patients with heterozygote mutations, fewer cases (13.6%) progressed to renal failure and/or ESRD than in with patients who had homozygote/compound heterozygote mutations (31.3%). In conclusion, podocin mutations are responsible for some of both familial and sporadic SRNS cases in Turkey. The mutations in this gene should be searched for in every child after presentation with the first episode of NS. [ABSTRACT FROM AUTHOR]

Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene −2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the −2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the −2518 (G/A) MCP-1 gene polymorphism ( p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA ( p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the −2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis ( p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine genotypic and allelic frequencies of macrophage migration inhibitory factor (MIF) gene −173 G/C polymorphism in patients with juvenile rheumatoid arthritis (JRA) and to evaluate the association of the MIF −173 C allele with the outcome of JRA. Genomic DNA was collected from 67 JRA patients and 153 healthy individuals. To evaluate the association of the MIF −173 polymorphism with the outcome, we analyzed the data concerning the treatment regimen, duration of glucocorticoid treatment, score on the childhood health assessment questionnaire (C-HAQ) and the number of joints with active arthritis. Nonsignificant differences were observed between the study and control groups in the distribution of genotype and allele frequencies of the MIF gene −173 G/C polymorphism. In JRA patients, carrying a MIF −173 C allele, the number of disease modifying antirheumatic drugs required for the treatment was more, the duration of glucocorticoid treatment was significantly longer, and at the last visits the C-HAQ scores and the number of joints with active arthritis were significantly higher. MIF gene −173 C allele frequency did not differ between the controls and JRA patients. MIF −173 C allele did not confer increased susceptibility to JRA in our study group. Carriage of the MIF −173 C allele was found to be a strong predictor of poor outcome in all types of JRA. [ABSTRACT FROM AUTHOR]

Abstract: 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 χ 2 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. [Copyright &y& Elsevier]

Objective: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. We aimed to evaluate the interleukin (IL)-6 gene polymorphisms in type 2 DN and control subjects. Materials and Methods: The patients selected from the Department of Endocrinology and Metabolism Diseases included 43 type 2 diabetes mellitus patients without DN and 43 type 2 diabetes mellitus patients with DN and 340 healthy normal controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, and insulin and Il-6 gene polymorphism genetic analysis. Results: IL-6 −174 G>C genotype distribution was different between the control group and the type 2 diabetes mellitus patients ( p=0.004). The higher frequency of the polymorphic G allele was also similar for the group with type 2 diabetes mellitus as for the control group. The frequency of the polymorphic G allele was 83.9% in diabetic patients with nephropathy versus 70.9% in those without nephropathy ( p=0.039). Conclusion: We suggest that the −174 G>C polymorphism of the IL-6 gene is an independent risk factor for DN in Turkish type 2 diabetes mellitus patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Henoch–Schönlein purpura (HSP) is a small-vessel vasculitis of autoimmune hypersensitivity with rash, arthritis, abdominal pain and renal involvements. Macrophage migration inhibitory factor (MIF) is a immunoregulatory proinflammatory cytokine, and a major mediator at the inflammatory sites. The pathogenesis of HSP has not been fully elucidated. Here we aimed to assess the influence of macrophage migration inhibitory factor gene (−173 G/C) polymorphism in the susceptibility and clinical expression of patients with Henoch–Schönlein purpura (HSP). HSP patients (n:139) and ethnically matched healthy controls (n:100) were genotyped by PCR–RFLP. Genotype analysis of both polymorphisms did not reveal a significant deviation from Hardy–Weinberg equilibrium in any group (p >0.05). No significant difference was obtained in genotype distribution (p >0.05) and allele frequencies (p >0.05) between patients and controls. A statistically significant genotype–phenotype correlation was not obtained when HSP patients were stratified by the presence of certain systemic complications and the macrophage migration inhibitory factor gene (−173 G/C) polymorphism (p >0.05). A significant risk was not observed in the subjects both with the GC+CC genotype (p =0.06, OR: 0.5538, 95% CI: 0.2985–1.0274) and C allele (odds ratio: C vs. G: 1.799, 95% CI: 1.002–3.23, p =0.05). Our findings suggest that MIF gene −173 G/C polymorphism is not associated with HSP in the present Turkish population. [Copyright &y& Elsevier]

Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis of autoimmune hypersensitivity, and renin-angiotensin system (RAS) regulates vascular homeostasis and inflammation with activation of cytokine release. Thus, we aimed to investigate the association between HSP and ACE I/D and AGT M235T polymorphisms. Genotyping was determined by allele specific PCR and PCR-RFLP. We obtained a significant difference in genotype distribution (p=0.003) and allele frequencies (p<0.001) of ACE I/D polymorphism between patients and controls, while no significant association was detected in genotype distribution (p> 0.05) and allele frequencies (p> 0.05) of the AGT M235T polymorphism. Risk assessment showed significant risk for HSP in the subjects both with the ID + DD genotype (p=0.019, OR: 2.288, 95% CI: 1.136-4.609) and D allele (OR: D vs. I: 2.0528, 95% CI: 1.3632-3.0912, p=0.001) while no significant risk was obtained for HSP in the subjects both with the MT + TT genotype (p=0.312, OR: 1.3905, 95% T vs. M: 1.065, 95% CI: 0.7326-2.6391) and T allele (OR: patients were stratified by the presence of certain systemic complications of HSP, no significant association was detected with ACE I/D, and AGT M235T polymorphisms. Our findings suggest that ACE I/D polymorphism is significantly associated with HSP susceptibility. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between SPP1 gene polymorphisms and nephrolithiasis. Materials and Methods: A total of 65 pediatric patients and 50 healthy controls were enrolled in this study. Two known polymorphisms of the SPP1 gene, c.240T > C and c.708C > T nucleotide substitutions, both of which were also known as synonymous aminoacid polymorphisms, D80D and A236A, respectively, at SPP1 gene cDNA level, were investigated. SPP1 gene polymorphism was evaluated using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. Results: In c.240T > C polymorphism, C allele frequency [Odds Ratio (OR), 2.13; 95% Confidence Interval (CI), 1.170 to 3.880; P = .013] and CC genotype distribution (OR, 2.946; 95% CI, 0.832 to 10.431; P = .094) and in c.708C > T polymorphism, T allele frequency (OR, 2.183; 95% CI, 1.197 to 3.980; P = .011) and TT genotype distribution (OR, 3.056; 95% CI, 0.861 to 10.839; P = .084) were found to be higher in the patient group. Conclusion: SPP1 polymorphisms were found to be associated with nephrolithiasis and it may be suggested that SPP1 gene polymorphism could be a useful marker for evaluation of the early genetic risk factor in childhood nephrolithiasis. [ABSTRACT FROM AUTHOR]

Background/aim: Autosomal recessive polycystic kidney disease is an inherited kidney disease. This study aims to detect rare and common DNA variants of the PKHD1 gene using next-generation sequencing (NGS) and to classify them in terms of being pathogenic according to The American College of Medical Genetics and Genomics., Materials and Methods: NGS analysis was performed on the DNA of 304 patients who were referred to Ege University Molecular Medicine Laboratory with suspected polycystic kidney disease., Results: As a result, a total of 82 different DNA variants, 16 of which were novel, were detected. The breakdown of the variants found is as follows: 73 (89.02%) were missense variants, six (7.32%) nonsense variants, two (2.44%) frameshift deletions, and one (1.22%) nonframeshift deletion. According to The American College of Medical Genetics and Genomics classification of these variants, 26 were benign (Class 5), two were likely benign (Class 4), 36 were of uncertain significance (Class 3), and nine were likely pathogenic (Class 2), nine of which are pathogenic variants (Class 1). Heterozygosity was found in 39 (63.9%) patients, homozygosity in six (9.8%) patients, compound heterozygosity in 12 (19.7%) patients, and complex genotype in four (6.6%) patients in which variants in Class 1, Class 2 and Class 3 were determined according to ACMG classification. When the exon distributions of the DNA variants detected in the PKHD1 gene were analyzed, the most common exons of the DNA variant are exon 32 (n = 9), exon 58 (n = 8), exon 67 (n = 6), exon 61 (n = 5), 30 exons (n = 4)., Conclusion: This fast and economical molecular diagnostic approach will provide a reliable prenatal diagnostic option, enabling definitive disease diagnosis and the identification of carriers., Competing Interests: Competing interests: The authors declare no competing interests., (© TÜBİTAK.)

Introduction: Atypical hemolytic uremic syndrome (aHUS) is associated with mutations or antibodies that affect the regulation of the alternative complement pathway. In the recent years several studies have been published describing these mutations. In this study, the initial clinical findings, treatments and long-term follow-up results of 19 patients who were hospitalized with the diagnosis of aHUS were presented., Materials and Methods: Nineteen patients who were diagnosed as aHUS were enrolled from January 2010 to March 2017. Initial clinical signs and clinical follow-up of patients with aHUS were evaluated. Disease causing complement factor H (CFH) mutations were determined.  Results. CFH mutations were detected in 5 of 19 aHUS cases. Of these, one was novel and 4 were previously reported. We reported here the clinical course of aHUS patients with CFH mutations (p.Glu936Asp, Val 1197Ala) and a novel mutation (Glu927Lys) which caused  previously defined aHUS. Two of the CFH mutation cases developed end stage kidney disease that required hemodialysis, 1 case developed chronic kidney disease. Two cases were in remission, one of them with supportive therapy and the other case was in remission with eculizumab treatment., Conclusions: Morbidity rate is higher in children with aHUS. The renal prognosis and morbidity rate is higher in children with CFH mutations than other children with aHUS. Poor prognosis in aHUS children with CFH mutation depends on the genetic background.

Sözeri B, Gerçeker-Türk B, Yıldız-Atıkan B, Mir S, Berdeli A. A novel mutation of interleukin-1 receptor antagonist (IL1RN) in a DIRA patient from Turkey: Diagnosis and treatment. Turk J Pediatr 2018; 60: 588-592. Autoinflammatory diseases can cause severe inflammation in bone and skin such as neonatal-onset multisystem inflammatory disease (NOMID), Majeed syndrome, interleukin-36 receptor antagonist deficiency (DITRA) and deficiency of interleukin-1 (IL-1) receptor antagonist (DIRA) syndrome. Here we report a five-year old boy who was admitted to the hospital with pustular skin lesions and fever in the first month of his life. Molecular analysis of IL1RN gene revealed a single homozygous C nucleotide deletion at nucleotide position 396 (p.Thr133Profs*118). The novel p.Thr133Profs*118 mutation found in our study caused frameshift mutation and as a result, the respective protein is most likely non-functional. The patient, who received a variety of treatments for various preliminary diagnoses until the final diagnosis (DIRA), was treated with recombinant IL-1Ra, anakinra, and experienced significant clinical improvement.

Objectives: To develop and assess the validity and reliability of an adherence scale concerning medical treatment in paediatric FMF patients., Methods: The Medication Adherence Scale in FMF Patients (MASIF) is a 18-item questionnaire that evaluates adherence to medication in four domains. Validation of the instrument was accomplished in paediatric FMF patients (aged 2-18 years) under medication at least for 6 months. The first step was to build up the scale through qualitative approach (with interviews using semi-structured questions). Validation analyses included assessment of feasibility, face and content validity; construct validity, internal consistency and test-retest reliability., Results: One hundred and fifty patients with FMF were enrolled in the study. The mean age of the patients was 11.11±4.02 years and 48.7% of them were male. The MASIF was found to be feasible and valid for both face and content. It correlated with the Morisky Medication Adherence Scale as a gold standard thereby demonstrating good construct validity (r=0.515, p<0.001). Assessment of content validity identified four subscales. The internal consistency, Cronbach's alpha was 0.728. There was a positive and significant correlation between test and retest scores (r=0.843; p<0.001). Also, a significant correlation between parents' and children's reports (r=0.781, p<0.001)., Conclusions: Based on these results, the use of this scale to assess and follow up the adherence to treatment in paediatric FMF patients under medical treatment is recommended.

Introduction: One of the genetic contributors to sarcopenia predisposition is Myostatin (MSTN), which in humans encodes myostatin, a 376 amino acid growth factor protein that negatively regulates muscle growth. The aim of this study was to investigate MSTN polymorphisms in an elderly sarcopenic population in Turkey and determine how they relate to sarcopenia., Materials and Methods: The study included nursing home residents who were aged ≥65 years. Sarcopenia screening was performed using "The European Working Group on Sarcopenia in Older People" guidelines. Blood sample was taken from each participant and DNA was obtained from the peripheral blood. MSTN polymorphisms were genotyped by polymerase chain reaction and restriction fragment length polymorphism methods., Results: A total of 152 elderly patients were included in the study. The rate of sarcopenia was determined to be 41.4%. The DNA nucleotide sequence of all three MSTN exons was determined for each study participant. Among the 152 patients, only 6 (3.9%) showed an MSTN K153R heterozygous mutation. Among these, three participants were sarcopenic and three were nonsarcopenic. No statistically significant difference in the polymorphism frequency between the sarcopenic and control groups was observed (p=0.664)., Conclusions: MSTN genotyping revealed that only 3.9% (6/152) of participants had the MSTN K153R heterozygous mutation. Despite the detection of this mutation in the study group, no relationship was found between this mutation and sarcopenia.

Variation in the gene encoding cyclooxygenase-1 (COX-1) is involved in the process of aspirin resistance. This study investigated the genetic variations in the COX-1 gene. The 4 coding regions of the human COX-1 gene in 90 pediatric patients (median age of 6.5 months, 55% males) with cardiovascular anomalies were screened using DNA sequencing. Twenty coding-region variants causing amino acid substitutions as well as 2 new non-synonymous polymorphisms were identified. All variants were compared with an independent Caucasian population (N = 24 unrelated individuals). Most of the discovered polymorphisms were rare, although some variants resulted in amino acid changes occurring at a frequency >5% (W8R, P17L, Q41Q, Q240Q, D189E, and P188P). In addition, 2 new non-synonymous polymorphisms (F200L and D189E) were identified. These findings demonstrated novel genetic variants of the human COX- 1 gene. Future studies characterizing the functional impact of these variants are warranted.

Background: It has been shown that toll like receptors (TLR) may be involved in some inflammatory skin diseases such as psoriasis, atopic dermatitis. Vitiligo is an acquired pigmentation disorder of unknown aetiology. A number of genes playing a role in inflammatory response may be associated with development of vitiligo., Objectives: To investigate whether there is an association between TLR 2 and TLR4 gene polymorphisms in Turkish patients with vitiligo., Methods: A total of 100 patients (59 women and 41 men) with vitiligo and 100 controls (58 women and 42 men) were included in the study. The TLR2 gene Arg753Gln and TLR4 gene Asp299Gly and Thr399Ile polymorphisms were genotyped by using polymerase chain reaction and restriction fragment length polymorphism method. The data were analysed by Mann-Whitney U-test, chi-squared test and logistic regression analysis., Results: Significant difference was found in the distribution of TLR2 Arg753Gln genotype and in the allele frequencies TLR2 753Gln between vitiligo patients and healthy subjects (P < 0.05). The distribution of TLR4 Asp299Gly genotype was significantly higher in the patient group (10%) than in the control group (%2) (P < 0.05). The TLR4 Thr399Ile distribution did not show any difference in both vitiligo and healthy groups., Conclusions: Our findings suggest that Toll-like receptor 2 gene Arg753Gln and Toll-like receptor 4 Asp299Gly gene polymorphisms are associated with vitiligo susceptibility in Turkish patients., (© 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.)

B lymphocyte subpopulations, previously defined classification schemes (Freiburg, Paris, EuroClass), TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF13 (APRIL) gene mutations, CTLA-4 and ICOS gene polymorphisms were analyzed in 25 common variable immunodeficiency (CVID) patients and 25 healthy controls. Patients were also divided into two subgroups due to some disease severity criteria. SG (severe disease group) (n:11) included patients who have splenomegaly and/or granulomatous diseases and/or bronchiectasis and/or lower baseline IgG values (<270 mg/dl). MG (moderate disease group) (n:14) patients diagnosed as having ESID/PAGID criteria but does not fulfill SG inclusion criteria. The onset of infectious symptoms and age at diagnosis were 50.0 ± 45.7 and 78.5 ± 54.5 months, respectively. Parental consanguinity rate was 54.5% in SG and 7.1% in MG. Switched-memory B cells (CD19 + 27 + IgD-IgM-) showed significant decrease in CVID patients and these cells were also significantly lower in SG compared to MG. CVID patients had significantly higher percentages of CD19 + κ + B cells and CD19 + λ + B cells than healthy controls. Freiburg classification: 87.5% of patients (n:21) were in group I and 12.5% were in Group II. Eighteen (75%) CVID patients with a low percentage of CD21(low) B cells were in Group Ib while three patients classified as Group Ia. The significantly lower levels of IgG and IgA in Group Ia is a novel finding. The percentages of patients for Paris Classification groups MB0, MB1, MB2 were 88%, 4% and 8%, respectively. There was a significant increase of splenomegaly, lymphadenopathy and autoimmune cytopenia in Group MB0. EuroClass: 45.8% of patients were smB+ and 54.2% were smB-. Splenomegaly and lymphadenopathy were significantly higher in smB- group. TACI: One patient carried heterozygous C104R mutation which was known as disease causing. APRIL: G67R and N96S SNPs were detected in most of the patients and healthy controls. BAFF-R: P21R/H159Y compound heterozygous mutation (n:1) and P21R heterozygous mutations (n:3) were detected. +49 A > G changes in exon 1 of CTLA-4 gene: GG and AG genotypes increase the risk of CVID development 1.32 and 2.18 fold, respectively. 1564 T > C polymorphisms on 3'UTR region in exon 2 of ICOS gene was not found to be significantly different in CVID patients. CVID classifications were not helpful in determining the genetic etiology of CVID.

Objective: Several gene polymorphisms have been reported to be associated with the risk of developing type 1 diabetes. Among them, the human leukocyte antigen locus is the strongest genetic determinant. To identify additional genetic markers, we aimed to evaluate the relationship between the Fas, Fas ligand (FasL), and vitamin D receptor (VDR) FokI gene polymorphisms and the susceptibility to type 1 diabetes in the Aegean region of Turkey., Materials and Methods: Eighty-five patients with type 1 diabetes and 80 healthy controls were included in this study. The Fas -670A/G, FasL -843C/T, and VDR FokI gene polymorphisms were evaluated using the polymerase chain reaction-restriction fragment length polymorphism method., Results: The evaluation of the Fas genotype and the gene allele frequency did not show statistically significant differences between the patient and control group. Distribution of the FasL genotype differed significantly between patients and controls. The distribution of the VDR FokI genotype and allele frequencies differed significantly between the patients and controls. Individuals with type 1 diabetes presented less commonly with the FokI f allele., Conclusions: Our findings suggest that the FasL -843C/T and VDR FokI gene polymorphisms are associated with type 1 diabetes in the Agean region of Turkey; however, the Fas -670A/G gene polymorphism is not.

Background: Severe combined immunodeficiency is within a heterogeneous group of inherited defects throughout the development of T- and/or B-lymphocytes. Mutations in recombinase-activating genes 1 or 2 (RAG1/2) represent approximately 10% of all SCID cases. RAG1/2 are essential for V(D)J rearrangement of the B- and T-cell receptors., Objectives: The aim of this study was to review clinical, immunological and molecular findings of Turkish SCID patients with RAG1 defects and to draw attention to novel mutations, genotype-phenotype correlations and the high rate of BCG infections within this group., Methods: Eleven patients (F/M: 6/5) were included. Molecular, immunological and clinical data were evaluated., Results: Five patients were classified as T-B-NK + SCID, four patients as T + B-NK + SCID (two of these patients were diagnosed as classical Omenn syndrome) and two patients as T + B + NK + SCID with respect to clinical presentations and immunological data. Mean age of the whole study group, mean age at onset of symptoms and mean age at diagnosis were: 33.0 ± 42.8, 3.1 ± 3.3 and 10.4 ± 13.5 months, respectively. Consanguinity rate was 54%. Some novel mutations were found in RAG1 gene in addition to previously reported mutations. Genotype-phenotype correlation was not significantly apparent in most of the cases. BCG infection was observed in 36.4% of patients (two BCG-osis and two BCG-itis)., Conclusion: Epigenetic factors such as compound genetic defects, enviromental factors, and exposure to recurrent infections may modify phenotypical characteristics of RAG deficiencies. Inoculation of live vaccines such as BCG should be postponed until primary immunodeficiency disease is excluded with appropriate screening tests in suspected cases.

Objective: 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., Research Design and Methods: 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., Results: 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 (p<0.001). The frequency of the mutant G allele was 36.1% in patients with diabetes nephropathy versus 39.6% in those without nephropathy (p>0.05). 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 (p>0.05)., Conclusions: 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.

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.

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., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Tissue macrophage accumulation is thought to induce insulin resistance during obesity and stimulate the progression of diabetic nephropathy (DN). The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene polymorphism in the healthy and patients with and without DN. The MCP-1 genotypes were determined in 43 patients with nephropathy and 43 without nephropathy and a control group of 105 healthy individuals. The genotype MCP-1 (-2518G/A) distribution did differ between the control group and the type 2 diabetic patients (P = 0.004). The frequency of the polymorphic G allele was also no similar for the group with type 2 diabetes as for the control group with 20.9 and 32.4%, respectively (P = 0.012). The AA genotype and A allele at MCP-1 -2518 was an independent risk factor for the progression of type 2 diabetes. In conclusion, MCP-1 AA genotype and A allele may play a specific role(s) in determining diabetic susceptibility, but do not seem to be important in the clinical manifestations of DN.

Background: The aims of the present study were: (1) to investigate mannose-binding lectin (MBL) gene exon-1 polymorphisms in Turkish subjects with chronic periodontitis (CP), (2) to assess the association between these polymorphisms and plasma MBL levels, (3) to determine the effects of MBL genotypes on the outcomes of non-surgical periodontal therapy., Methods: A total of 172 subjects were included in the present study. Genomic DNA was obtained from the peripheral blood of 83 CP patients and 89 periodontally healthy subjects. The MBL levels were measured by enzyme-linked immunosorbent assay (ELISA). The MBL gene exon-1 polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method., Results: Subjects homozygous for the frequent allele A had higher MBL plasma levels compared with rare allele B carriers. This difference in MBL plasma levels was statistically significant both in CP patients and healthy subjects. The distribution of MBL gene codon 54 genotypes and allele frequencies did not differ significantly between study groups. All study subjects were the MBL gene codon 52 and 57 frequent allele A carriers. Codon 54 B allele carriers had similar clinical periodontal parameters compared with AA genotypes after non-surgical periodontal therapy., Conclusions: The present study failed to find any significant association between the MBL gene codon 54 polymorphisms and severe CP in a Turkish population. MBL gene rare allele carriers had lower MBL plasma levels in both study groups. It seems that MBL gene codon 54 B allele carriage may not influence the outcome of periodontal therapy., (Copyright 2010. Published by Elsevier Ltd.)

Chronic allograft nephropathy (CAN) is a complex phenomenon caused by underlying kidney disease with superimposed enviromental and genetic factors. CAN development begins with progressive renal microvascular injury. Endothelial cells play key roles in the regulation of vascular tone, permeability, and remodeling. A reduction in basal nitric oxide (NO) release as a result of genetic variation in endothelial NO synthase (eNOS) function may predispose to hypertension, thrombosis, vasospasm, and atherosclerosis, all contributing to the development of CAN. We analyzed the G894T mutation at exon 7 of the eNOS gene in relationship to CAN among 81 children with renal transplantations. The 20 patients who developed CAN underwent renal biopsies for histological confirmation. Proteinuria and hypertension were observed in CAN. We selected 173 healthy reference subjects. The G894T polymorphism of the eNOS gene was determined by PCR-restriction fragment-length polymorphism analysis. The group included 33 male and 48 female subjects who received 32 living-related grafts and 49 from deceased donors (DD) donors. Donor age (y) was 32.7 +/- 13.7 and the HLA A,B,DR mismatch number of the cadaveric cases was 3.5 +/- 0.79. The distribution of the genotypes were ENOS GG/GT/TT 48%, 33%, 19%, respectively. G-alleles frequency was 64.8%; T-allele frequency was 35.2%. ENOS G894T gene polymorphism did not seem to influence long-term renal allograft outcome. Recipient ENOS G894T gene polymorphism did not alter the risk of chronic allograft failure. Even if NO synthesis and bioactivity are influenced by this polymorphism, many vasoactive factors may have roles to suppress the advantageous effects of NO.

We aimed to evaluate the relationship between 174 promoter region of the interleukin-6 (IL-6) C/G gene polymorphism and high sensitive C-reactive protein (hs-CRP), fibrinogen and carotis intima-media thickness (CIMT), body mass index, homeostatic model assessment (HOMA) insulin resistance index, serum lipid parameters, in polycystic ovary syndrome (PCOS) patients carrying a potential risk for developing cardiovascular disease (CVD). We studied 88 PCOS patients and 119 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria. The genotype IL-6 distribution did differ between the control group (CC 10.1%, GC 63.0%, GG 29.6%) and the PCOS patients (CC 5.7%, GC 29.5%, GG 64.8%) (P < 0.001). The frequency of the polymorphic G allele was also no similar for the group with PCOS as for the control group with 79.5% and 58.4% respectively (P < 0.001). Both in PCOS patients and in control group, no statistically significant difference was determined between C/C, G/C and G/G, and blood cholesterol levels, triglyceride levels, high-density lipoprotein levels, low density lipoprotein levels, fasting blood sugar levels, insulin levels, HOMA values, CIMT measurements either on the right or left side, hs-CRP, f-testosterone, fibrinogen and 17 alpha-hydroxy-progesterone levels (P > 0.05). Gene polymorphism of IL-6 -174 G>C is a risk factor for PCOS in Turkish patients, but we found no relationship between the cardiovascular risk factors and IL-6 -174 G>C gene polymorphism in women with PCOS and healthy subjects. Our negative results in risk factors of CVD can probably be explained by the fact that metabolic parameters and endothelial systems of patients may not yet be affected in this short time of period.

Introduction: Interleukins and cytokines play an important role in the pathogenesis of many cancers.We aimed to evaluate the interleukin (IL)-6 gene polymorphisms in patients with papillary thyroid carcinoma (PTC) and control subjects., Material and Methods: In this study, 42 patients with PTC and 340 healthy controls were included. Peripheral blood samples were taken from control group and patients, and blood samples were preserved at -80 C in tubes containing Na-EDTA., Results: We also found a statistically significant difference between patients with PTC and the control group with respect to IL-6 genotype (p<0.05). IL-6 gene polymorphism in patients with PTC patients did not reveal statistically significant difference between the 2 groups (size of tumor >1 cm and <1 cm), multicentricity, RET-PTC types and capsule invasion (p>0.05).We also did not find a statistically significant difference between patients with PTC and the control group with respect to IL-6-gene allele frequency (p>0.05)., Discussion: Our data suggest that the IL-6 G-174 C polymorphism could play a role in thyroid cancer risk, but there is no effective role as a prognostic factor.

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.

Aim: 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)., Methods: 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., Results: Both ACE I/D and AT1R polymorphisms were similar in G-AgP and healthy groups (p>0.05). G-AgP subjects exhibited decreased AGT TT genotype and T allele frequency as compared to healthy subjects (p<0.05). The same trend was also observed in the nonsmoker subgroup regarding investigated RAS polymorphisms., Conclusions: Present findings suggest that AGT M235T TT genotype and T allele might be associated with decreased risk for G-AgP in Turkish population.

Objective: G protein is one of the most important regulators of intracellular signaling pathways. C825T polymorphism of G protein b3 subunit is associated with increased intracellular signal transduction. The 825T allele has been found associated with a variety of cardiovascular risk factors, including hypertension. The aim of the present study was to investigate the association between the C825T polymorphism of the G protein b3 subunit and essential hypertension in Turkish population., Methods: This cross-sectional, case-controlled study included 209 patients with essential hypertension (Patient group) and 82 subjects with normal blood pressure (Control group). The G protein b3 subunit C825T gene polymorphism was determined by polymerase chain reaction. Hypertension was defined according to JNC VII criteria. Statistical analysis was performed using Chi square and unpaired t tests. Logistic regression analysis was used to study association between hypertension and genotypes., Results: We found that the frequencies of the G protein b3 subunit C825T polymorphism in hypertensive and control groups were 17.7%, 59.3%, 23.0% and 32.9%, 48.8%, 18.3%, (CC, CT, TT) respectively (chi2=7.963, p=0.019). In the multivariate logistic regression analysis CT genotype had 2.2 (OR=2.262, 95% CI 1.228-4.167, p=0.009), and TT genotype had 2.3 times (OR=2.335, 95% CI 1.089-5.008, p=0.029) greater risk of hypertension compared to CC genotype., Conclusion: It seems that the G protein b3 subunit C825T gene polymorphism is associated with systolic and diastolic blood pressure. Furthermore, the study indicates that the G protein b3 subunit may be a susceptible gene to essential hypertension.

Objective: Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular (CD) diseases. Cardiovascular risk factors that have been reported include oxidative stress markers [nitric oxide (NO), malondialdehyde (MDA), disulphite (SH)]. We aimed to evaluate the relation between the IL-6 G/C gene polymorphism and oxidative stress markers in polycystic ovary syndrome (PCOS) patients., Design and Patients: We studied 85 PCOS patients and 115 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria., Results: The genotype IL-6 distribution did differ between the control group (CC 9.6%, GC 63.4%, GG 27.0%) and the PCOS patients (CC 4.7%, GC 29.4%, GG 65.9%) (p<0.001). The frequency of the polymorphic G allele was also not similar for the group with PCOS as for the control group with 80.6% and 58.7%, respectively (p<0.001). No statistically significant difference was determined for MDA and NO levels in PCOS patients and control group (p>0.05). Only SH levels were found to be high in favor of patient group (p<0.05). No statistically significant difference was determined between IL-6 G/C gene polymorphism and oxidative stress markers in PCOS patients and in the control group., Conclusion: Gene polymorphism of IL-6 -174 G>C is a risk factor for PCOS in Turkish patients. IL-6 gene polymorphisms are not related to NO, MDA, and SH levels in PCOS. Our negative results in risks factors of CV disorders can probably be explained by the fact that metabolic parameters and endothelial systems of patients may not yet be affected in this short period of time.

Objective: In recent years, thyroid cancer has been at the forefront of molecular pathology as a result of the consequences of the Chernobyl disaster and the recognition of the role of RET/PTC rearrangements in papillary thyroid carcinomas (PTCs). Correlation of RET/PTC expression with clinical outcome is controversial. This study aims to identify the prevalence of RET/PTC oncogene expression in Turkey, and to investigate the correlation between RET/PTC oncogene expression and the known prognostic factors of PTC in 101 patients., Methods: The RET rearrangements were examined by means of reverse transcriptase-polymerase chain reaction analysis, with primers flanking the chimeric region. Statistical evaluation was performed by using Independent samples t-test, One-sample Chi-square test and Pearson Chi-square or Fisher's Exact Test., Results: RET/PTC was determined positive in 67(66.3%) of totally 101 patients (p<0.001). RET/PTC1 in 32(31.7%), RET/PTC3 in 21(20.8%), RET/PTC1+RET/PTC3 both in 10(9.9%) patients were found to be positive. There was RET/PTC2 positiveness in two patients, RET/PTC2,3 positiveness in one patient, and RET/PTC1,2,3 positiveness in one patient. No statistical difference was found between RET/PTC1 and RET/PTC3. None of genetico-clinical analyses showed any significant association between RET/PTC expression and the clinical and pathological features of the cancers., Conclusion: While this prevalence of the RET/PTC is less than RET/PTC frequency seen after Chernobyl in Belarus, its prevalence in our region is also high (66.3%). As a result, no significant correlation was found in between prognosis and RET/PTC frequency.

Objectives: It has been suggested that monocyte chemoattractant protein-1 (MCP-1) is important in the initiation of atherosclerosis and crucial in monocyte recruitment into the subendothelial lesions. Recent studies have demonstrated that MCP-1 -2518 A>G polymorphism is associated with susceptibility to coronary artery disease (CAD). Since there are conflicting reports on the possible association of MCP-1 -2518 A>G polymorphism with CAD, we investigated the role of this polymorphism in Turkish patients with premature CAD., Material and Methods: Genomic DNA was collected from 171 premature CAD patients and 151 healthy individuals. MCP-1 -2518 A>G polymorphism was genotyped using the PCR-RFLP method., Results: There were no differences between genotype distribution and allele frequencies in the premature CAD and control groups (AA: 49.7 %; AG: 40.3 %; GG: 10.0 % in premature CAD groups and AA: 53.7 %; AG: 34.4 %; GG: 11.9 % in controls; p = 0.53). The prevalence of the G allele was 0.302 in patients and 0.291 in controls., Conclusions: Our data demonstrate that MCP-1 -2518 A>G polymorphism is not associated with premature CAD in Turkish patients. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of CAD in various populations.

The aim of this study is to investigate Arg753Gln allele polymorphisms of toll-like receptor-2 (TLR2) gene distribution, allele frequency in urinary tract infection (UTI) and genotype-phenotype association of TLR2 gene in children with UTI. The polymorphism was investigated in 124 children with UTI (22 boys and 102 girls; mean age 5.81 +/- 3.47 years) with direct DNA sequencing-based method. TLR2 gene Arg753Gln allele frequency was higher in the patient group when compared with control group (OR 3.14, 95%CI 1.53-6.44, P < 0.001). The frequency of the Arg753Gln allele was significantly higher in gram-positive group than in gram-negative group (OR 7.64, 95%CI 2.80-20.81, P < 0.001). The frequency of UTI was found significantly higher in the Arg753Gln allele carriers of TLR2 gene than the non-carriers (OR 4.94, 95%CI 1.09-22.33, P < 0.05). Similarly, the incidence of asymptomatic UTI was also found significantly higher in the group carrying Arg753Gln allele (OR 3.73, 95%Cl 1.54-9.04, P < 0.05). As a result, we suggest that TLR2 gene could be the predisposing factor for urinary tract infection. Additionally, we observed that subjects carrying the TLR2 Arg753Gln allele had higher risk of urinary tract infection with gram-positive pathogens, history of more than two attacks of UTI and asymptomatic UTI.

Purpose: Polycystic ovary syndrome (PCOS) is one of the most encountered endocrine malfunctions. PCOS patients have enhanced activation of the blood coagulation system., Methods: Eighty-six young women with PCOS and 70 healthy control women were included in our study. PCOS patients and controls were matched for age, body mass index, and allele frequency. Genetic analysis of TPAI and PAI-1 were performed in all subjects., Results and Conclusions: No statistically significant differences have been detected about the ratios of genotypes resulting from PAI-1 promotor 4G/5G gene polymorphism. PAI-1 765 4G/5G gene polymorphism and TPA gene's Alu-repeat insertion/deletion (I/D) polymorphism ratios were not different from the controls. In this study it is shown by the analysis of TPA gene's Alu-repeat insertion/deletion (I/D) polymorphism the PCOS patients with genotype II had lowers total cholesterol and LDL-cholesterol levels.

Polymorphisms in toll-like receptors (TLRs) have been reported to increase susceptibility for some diseases. TLR-2 gene polymorphisms in Turkish children with recurrent respiratory tract infections and without well-known humoral immunodeficiencies were examined. The study consisted of 52 children with recurrent infections (study group) and 91 healthy children with a maximum of two infections in a year (control group). Recurrent infection was defined as the presence of at least six febrile bacterial infection episodes in a year. Not only TLR-2 gene polymorphisms but also immunoglobulins (IgG, IgM, IgA), IgG subsets (G1, G2, G3), and specific antibody levels (anti-tetanus and anti-hemophilus influenza) were determined to exclude humoral immunodeficiencies. The Arg753Gln and Arg677Trp polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism. The Arg753Arg genotype was significantly decreased in the study group compared to the control (P < 0.05). Children with recurrent infections were also found to be more frequently Arg753Gln heterozygous (P < 0.05), and their Gln allele distribution was higher than that of the control subjects (23% vs. 4.9%; P < 0.001). In contrast to these results, we did not detect any case with Arg677Trp polymorphism in both groups. These results have indicated that there is a strong significant relationship between susceptibility to recurrent bacterial infections and Arg753Gln polymorphism of the TLR-2 gene.

Objectives: Interleukin-6 (IL-6) may contribute to the inflammatory response by activating endothelial cells and stimulating the synthesis of fibrinogen. It might thus be important in the pathogenesis of inflammation associated with coronary artery disease (CAD). Several studies suggested that the -174 C allele was associated with an increased prevalence of coronary heart disease. The aim of this study was to investigate further the association of the IL-6 -174 G/C allele status with premature CAD., Methods: A total of 120 patients and 105 controls were included in the study. The IL-6 -174 G/C polymorphism was genotyped using PCR-restriction fragment length polymorphism., Results: The genotype distribution of the -174 G/C polymorphism was not different in premature CAD patients (GG: 53%; GC: 42.6%; CC: 4.3%) and controls (GG: 54.3%; GC: 39%; CC: 6.7%) (P=0.72). The prevalence of the C allele was 25.6% in patients and 26.1% in controls. By multiple regression analysis, family history, smoking, diabetes, and hypertension were independent risk factors of premature CAD, but not IL-6 genotype., Conclusions: We conclude that the IL-6 -174 G/C polymorphism is not associated with the risk of premature CAD, and does not contribute to cardiovascular risk stratification.