Novel SNARE Complex Polymorphisms Associated with Multiple Sclerosis: Signs of Synaptopathy in Multiple Sclerosis

Background: It is well known that axonal degeneration plays a role in disability in patients with multiple sclerosis, and synaptopathy has recently become an important issue.Aims: To investigate the possible roles of selected synaptic and presynaptic membrane protein genetic polymorphisms (VAMP2, SNAP-25, synaptotagmin, and syntaxin 1A) in patients with multiple sclerosis.Study Design: Case-control study.Methods: A total of 123 patients with multiple sclerosis and 192 healthy controls were included. The functional polymorphisms of specific SNARE complex proteins (VAMP2, synaptotagmin XI, syntaxin 1A, and SNAP-25) were analyzed by polymerase chain reaction.Results: Significant differences were detected in the genotype and allele distribution of 26-bp Ins/Del polymorphisms of VAMP2 between patients with multiple sclerosis and control subjects; Del/Del genotype and Del allele of VAMP2 were more frequent in patients with multiple sclerosis (p=0.011 and p=0.004, respectively). Similarly, Ddel polymorphism of SNAP-25 gene C/C genotype (p=0.059), syntaxin 1A T/C and C/C genotypes (p=0.005), and synaptotagmin XI gene C allele (p=0.001) were observed more frequently in patients with multiple sclerosis. CC, syntaxin rs1569061 1A gene for 33-bp promoter region TC haplotypes, and synaptotagmin XI gene were found to be associated with an increased risk for multiple sclerosis (p=0.012). Similarly, GC haplotype for rs3746544 of SNAP-25 gene and rs1051312 of SNAP-25 gene were associated with an increased risk for multiple sclerosis (p=0.022).Conclusion: Genetic polymorphisms of SNARE complex proteins, which have critical roles in synaptic structure and communication, may play a role in the development of multiple sclerosis

Homozygous Ala65Pro Mutation with V89L Polymorphism in SRD5A2 Deficiency

Objective: Deficiency of steroid 5-alpha reductase type 2 (5?RD2) is a rare autosomal recessive disorder caused by mutations in the SRD5A2 gene. A defect in the 5-alpha reductase enzyme, which ensures conversion of testosterone into dihydrotestosterone, leads to disorders of sex development. This study presents the clinical and genetic results of patients with 5?RD2 deficiency. Methods: 5?RD2 deficiency was detected in 6 different patients from 3 unrelated families. All patients were reared as girls. Two of the patients presented with primary amenorrhea, one with primary amenorrhea and rejection of female gender, and the others with masses in their inguinal canals. Chromosome and sex-determining region Y (SRY) gene analyses were performed in all patients. Additionally, five exons of the SRD5A2 gene were amplified with polymerase chain reaction in the obtained DNA samples and evaluated. Results: While 46,XY was identified in 5 patients, 47,XXY was detected in one patient. The SRY gene was positive in all patients. The p.Ala65Pro (c193G>C) mutation and V89L polymorphism were observed in exon 1 of the SRD5A2 gene in all patients. Conclusion: Identification of this mutation and polymorphism is a significant indicator of presence of 5?RD2 deficiency in Southeastern Turkey, a geographical region where consanguineous marriages are also highly common.Objective: Deficiency of steroid 5-alpha reductase type 2 (5?RD2) is a rare autosomal recessive disorder caused by mutations in the SRD5A2 gene. A defect in the 5-alpha reductase enzyme, which ensures conversion of testosterone into dihydrotestosterone, leads to disorders of sex development. This study presents the clinical and genetic results of patients with 5?RD2 deficiency. Methods: 5?RD2 deficiency was detected in 6 different patients from 3 unrelated families. All patients were reared as girls. Two of the patients presented with primary amenorrhea, one with primary amenorrhea and rejection of female gender, and the others with masses in their inguinal canals. Chromosome and sex-determining region Y (SRY) gene analyses were performed in all patients. Additionally, five exons of the SRD5A2 gene were amplified with polymerase chain reaction in the obtained DNA samples and evaluated. Results: While 46,XY was identified in 5 patients, 47,XXY was detected in one patient. The SRY gene was positive in all patients. The p.Ala65Pro (c193G>C) mutation and V89L polymorphism were observed in exon 1 of the SRD5A2 gene in all patients. Conclusion: Identification of this mutation and polymorphism is a significant indicator of presence of 5?RD2 deficiency in Southeastern Turkey, a geographical region where consanguineous marriages are also highly common

Türk populasyonununda tip 2 diabet hastalarında insülin substrat-2 geni g1057d polimorfizmi

Amaç: İnsülin reseptör substratı (IRS) proteini, hedef dokulara insülin sinyalinin iletilmesinde kritik bir öneme sahiptir. IRS-2 knockout farelerin insanlardaki tip 2 diabete benzer bir klinik fenotip gösterdiği tespit edilmiştir. IRS2 geninde çok sayıda polimorfizm belirlenmiş olmakla birlikte farklı populasyonlarda tip 2 diabet ile IRS-2 Gly1057Asp polimorfizmi arasındaki ilişki araştırılmış olup elde edilen sonuçlar oldukça çelişkilidir. Bu çalışmada Türk populasyonunda Diabetes mellitus ile IRS-2 G1057D polimorfizmi arasındaki ilişkiyi araştırmak amaçlanmıştır. Materyal ve Metot: Çalışma populasyonu 328 kişiden oluşmakta olup 138 kişi DM hastası ve 190 kişide kontroldür. DNA periferik kandan izole edilmiş olup IRS2 G1057D polimorfizmi PCR-RFLP yöntemi kullanılarak belirlenmiştir. Bulgular: IRS2 G1057D polimorfizmi genotip dağılımlarının gruplar arasında istatistiksel olarak anlamlı bir farklılık göstermediği tespit edilmiştir. Sonuçlar: Elde edilen bulgular IRS2 G1057D polimorfizminin tip 2 diabetin patogenezinde rolü olmadığını göstermektedir.Background: Insulin receptor substrate (IRS) proteins are critical to signal transduction in insulin target tissues. IRS-2 knockout mice exhibit a phenotype similar to human type 2 diabetes, characterized by insulin resistance with abnormal glucose tolerance at birth culminating in the development of fasting hyperglycemia in later age. While several polymorphisms have been identified in the IRS-2 gene, the association of the Gly1057Asp polymorphism with type 2 diabetes has been studied in different populations, but the results have been inconsistent. The present study was undertaken to determine IRS-2 G1057D polymorphism association with Diabetes mellitus in Turkish subjects. Material and Methods: The study population consisted of 328 subjects 138 patients with DM and 190 controls. DNA was extracted from peripheral blood. Genetic polymorphism of IRS-2 G1057D was detected by using PCR-based restriction fragment-length polymorphism. Results: The genotype distribution of the IRS2 G1057D polymorphism was not statistically significant between groups. Conclusions: These results strongly argue against a major role of the G1057D IRS-2 polymorphism in the pathogenesis of type 2 diabetes in Turkish subjects

Critical thinking disposition of nursing students and affecting factors

Amaç: Bu araştırmanın amacı hemşirelik öğrencilerinin eleştirel düşünme eğilimlerini ve etkileyen faktörleri belirlemektir. Yöntemler: Kesitsel tipte tanımlayıcı araştırma, Bülent Ecevit Üniversitesi Hemşirelik Bölümü öğrencileriyle (n=323) gerçekleştirildi. Veriler Kişisel Bilgi Formu ve Kalifornia Eleştirel Düşünme Eğilimi Ölçeği ile toplandı. Veriler sayı, yüzde, ortalama, standart sapma, student t testi, tek yönlü ANOVA testi, Mann Whitney U testi, Kruskal Wallis testi ve Pearson Korelasyon analizi ile değerlendirildi. Bulgular: Öğrencilerin eleştirel düşünme eğilimi puan ortalamaları 239.70±27.24 olarak belirlendi. Bayan öğrencilerin (p=0.03), ikinci sınıf öğrencilerinin (p=0.002), öğrenci kulüplerine üye olan (p=0.007), kitap okumayı seven (p=0.000), kütüphaneye giden (p=0.03), yılda 4 ve üzeri bilimsel etkinliğe katılan öğrencilerin (p=0.002) eleştirel düşünme eğilimleri toplam puan ortalamasının en yüksek olduğu bulundu. Sonuç: Hemşirelik öğrencilerinin eleştirel düşünme eğilimlerinin düşük düzeyde olduğu ve yaş, cinsiyet, sınıf, kitap okuma, kütüphaneye gitme gibi demografik özelliklerinin eleştirel düşünme eğilimlerini etkilediği saptandıThe purpose of this study was to determine the dispositionsof critical thinking of nursing students and affecting factors.Methods:This cross-sectional descriptive study wasconducted with Nursing Department students (n= 323) of Bulent Ecevit University. Data werecollected by Personality Survey Form and The California Thinking Disposition Inventory. Data wereevaluated by percentage, mean, standard deviation, student t test, one way ANOVA, Mann Whitney U test, Kruskal Wallis, and Pearson correlation analyze.Results:The critical thinking disposition mean score of the nursing students wasdetermined as 239.70±27.24.It was found that female students(p=0.03), 2ndyear students (p=0.002), studentswho are members ofclubs(p=0.007), students who like to read the book (p=0.000) students who are going to library (p=0.03), students who have participated four and more scientific activity (p=0.002)a year were higherthe dispositions of critical thinking.Conclusion:It wasfound that nursing students had low levelthe critical thinking disposition and had demographic features such as age, gender, class, like to read the book and go to library of nursing students wereeffect the critical thinking disposition

Association of IL2-330 Gene Polymorphism with Lung Cancer

Cytokines are secreted or membrane-bound proteins that act as mediators of intercellular signaling to regulate homeostasis of the immune system. They are produced by cells of innate and adaptive immunity in response to microbes and tumor antigens. Although there are several studies showing that IL2-330 gene polymorphism is associated with many types of cancer, as far as we know, there is a few study investigating the association between lung cancer and IL2-330 gene polymorphism. In this study, the role of IL2-330 gene polymorphism in the pathogenesis of lung cancer was investigated. 96 patients who were diagnosed with lung cancer and 96 age and sex matched healthy subjects participated in the study. Genomic DNA was isolated using the blood DNA isolation kit and the IL2-330 gene polymorphism was determined by polymerase chain reaction-confronting two pairs primer method. When analyzed for the lung cancer group and the healthy group according to IL2-330 gene polymorphism, genotype and allele frequencies were found to be similar in both groups (p>0,05). As a result; there was no statistically significant difference between the groups. Considering the ethnic diversity of lung cancer, the study needs verified in other populations

Investigation of IL-1 Beta, IL-1 receptor antagonist and IL-8 gene polymorphisms in patients with chronic hepatitis B and C

Hepatit B ve C virusu (sırasıyla; HBV ve HCV) enfeksiyonlarında hastalığın prognozu ve viral persistans konağın immün yanıtı ile yakından ilişkilidir. Sitokinler ve genetik faktörler, kronik HBV ve HCV enfeksiyonlarının patogenezinde önemli rol oynarlar; ancak altta yatan moleküler mekanizmalar tam olarak anlaşılamamıştır. Bu çalışma, kronik hepatit B ve C hastalığı ile interlökin (IL)-1?, IL-1 reseptör antagonisti (IL-1RA) ve IL-8 gen polimorfizmleri arasındaki ilişkinin belirlenmesi amacıyla yapılmıştır. Çalışmaya, kronik hepatit B’li 171 hasta (62 kadın, 109 erkek; yaş aralığı: 18-74 yıl), kronik hepatit C’li 104 hasta (63 kadın, 41 erkek; yaş aralığı: 25-79 yıl) ve kontrol olarak 86 sağlıklı kişi (41 kadın, 45 erkek; yaş aralığı: 18-72 yıl) olmak üzere toplam 361 olgu dahil edilmiştir. Olguların periferal kan lökositlerinden DNA ekstraksiyonu sonrası, IL-1? -31, -511, +3954; IL-1RA ve IL-8 -251, -353, -738, -845 gen bölgelerine özgül primerler kullanılarak tek nükleotid polimorfizmleri gerçek zamanlı PCR yöntemi ile araştırılmıştır. Kronik hepatit B’li hastalarda IL-8 -251 AT (OR: 7.895, p= 0.003) ve IL-8 -738 TA (OR: 6.317, p= 0.007) genotip sıklığı; kronik hepatit C’li hastalarda ise IL-1? -31 CT (OR: 6.757, p= 0.001), IL-1? -511 CT (OR: 4.060, p= 0.004), IL-8 -251 AT (OR: 13.622, p= 0.001), IL-8 -738 TA (OR: 14.058, p= 0.001) ve IL-8 -845 TC (OR: 2.539, p= 0.004) genotip sıklığı kontrol grubuna göre anlamlı düzeyde yüksek bulunmuştur. Kronik hepatit B’li hastalardaki allel sıklığı kontrol grubu ile kıyaslandığında; IL-1? +3954 T allelinin hastalık riskini 1.5 kat artırdığı belirlenmiş (p 0.05). Kronik hepatit C’de ise IL-8 -845 C allelinin hastalık riskini 0.6 kat artırdığı (p 0.05). Sonuç olarak IL-1? -31, -511 promotor gen bölgesindeki polimorfizmler ve IL-8 -251, -738, -845 gen polimorfizmleri HBV ve HCV enfeksiyonlarının kronikleşmesinde etkili olabilir. Bu sitokin polimorfizmlerinin, kronik hepatit B ve C enfeksiyonlarındaki öneminin belirlenebilmesi için, taşıyıcı, kronik hepatit, siroz ve hepatoselüler karsinoma gibi farklı hasta gruplarını içeren daha büyük ölçekli çalışmalar, moleküler mekanizmaların aydınlatılmasına katkı sağlayabilir.The host immune response is closely related to the prognosis of disease and viral persistence in hepatitis B (HBV) and hepatitis C virus (HCV) infections. Althought it is well known that cytokines and genetic factors play important roles in the pathogenesis of chronic HBV and HCV infections, the underlying mechanisms are not fully understood. This study was conducted to determine the role of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA) and IL-8 gene polymorphisms in chronic hepatitis B and C infec- tions. A total of 361 subjects, 171 with chronic hepatitis B (62 female, 109 male; age range: 18-74 yrs) and 104 with chronic hepatitis C (63 female, 41 male; age range: 25-79 yrs), and a control group of 86 healthy subjects (41 female, 45 male; age range: 18-72 yrs) were included in the study. Following the DNA extractions from peripheral blood leukocytes of the study groups, single nucleotide polymor- phisms of IL-1β -31, -511, +3954; IL-1RA and IL-8 -251, -353, -738, -845 gene regions were investigated by using specific primers with real-time PCR method. It was found that the genotype frequency of IL-8 -251 AT (OR: 7.895, p= 0.003) and IL-8 -738 TA (OR: 6.317, p= 0.007) in patients with chronic hepatitis B and the genotype frequency of IL-1β -31 CT (OR: 6.757, p= 0.001), IL-1β -511 CT (OR: 4.060, p= 0.004), IL-8 -251 AT, (OR: 13.622, p= 0.001), IL-8 -738 TA (OR: 14.058, p= 0.001), and IL-8 -845 TC (OR: 2.539, p= 0.004) in patients with chronic hepatitis C was significantly higher than the control group. When the allelic frequency was compared between chronic hepatitis B patients and the control group, it was determined that IL-1β +3954 T allel increased the disease risk 1.5 times (p 0.05). In conclusion, IL-1β -31, -511 and IL-8 -251, -738, -845 gene polymorphisms may play a role in the chronicity of hepatitis B and C infection. In order to determine the importance of this cytokine polymorphisms in hepatitis B and hepatitis C virus infections, large-scale studies with different patient groups such as carriers, chronic hepatitis, cirrhosis, and hepatocellular carcinoma should be conducted to elucidate the molecular mechanisms underlying the disease process

Relationship between gastric cancer and SULT1A1 R213H gene polymorphism

Giriş ve Amaç: Ülkemizde gastrointestinal sistem kanserleri, akciğer kanserinden sonra en sık görülen kanserlerden birisidir. Mide kanseri ise gastrointestinal sistem kanserlerinin en sık rastlanılan tümörüdür. Yapılan çalışmalar, ksenobiyotik metabolizmasından sorumlu genler- deki polimorfizmlerin bireylerin kanser riskini değiştirebileceği üzerine yoğunlaşmaktadır. Sülfotransferazlar, ksenobiyotik metabolize eden enzim grubunda bulunmakta olup, bu enzim grubu endojen ve eksojen kimyasalların detoksifikasyonu ve biyoaktivasyonunda rol oynamakta- dırlar. Bu çalışmada SULT1A1 gen polimorfizmi ile mide kanseri ara- sında ilişkinin araştırılması amaçlanmıştır. Gereç ve Yöntem: SULT1A1 geni R213H polimorfizmi 59 mide kanseri hastası ve 80 kontrol bireyde polimeraz zincir reaksiyonu/restriksiyon parça uzunluğu polimorfizmi yöntemi kullanılarak belirlenmiştir. Bulgular: Kontrol grubu ile hasta grubunu oluşturan mide kanserli bireyler karşılaştırıldığında, SULT1A1 Arg/His genotipini taşımanın mide kanseri açısından koruyucu etki gös- terdiği tespit edilmiştir (p=0.017). Ayrıca sigara içmeyen bireylerde Arg/ His genotipinin koruyuculuk etkisinin daha da belirginleştiği dikkat çek- mektedir. Sonuç: Sonuç olarak elde edilen bulgular SULT1A1 His poli- morfizmini heterozigot taşıyan bireylerin mide kanseri patogenezinde rol oynayan karsinojenlere karşı daha iyi bir koruma sistemleri olduğunu göstermektedir.Background and Aims: After lung cancer, gastrointestinal cancer is one of the most common cancers in our country. Gastric cancer is the most common gastrointestinal cancer. Recent studies have been fo- cused on polymorphisms in genes responsible for xenobiotic metab- olism that may alter the risk of cancer. Sulfotransferases are in the group of xenobiotic metabolizing enzymes involved in the bioactiva- tion and detoxification of endogenous and exogenous chemicals. In this study, we aimed to investigate the relationship between SULT1A1 gene polymorphisms and gastric cancer. Material and Methods: SULT1A1 R213H gene polymorphisms were determined in 59 gastric cancer patients and 80 control subjects by using polymerase chain re- action-restriction fragment length polymorphism. Results: Our results indicate that SULT1A1Arg/His genotype carriers have increased protec- tion against gastric cancer compared with the control group. In addi- tion, it is noteworthy that the protective effect of the Arg/His genotype is more pronounced in non-smoking individuals. Conclusion: These findings suggest that heterozygous individuals for the SULT1A1 R213H polymorphism have better protection against carcinogens that play a role in the pathogenesis of gastric cancer

Variant Analysis of the Sirtuin (SIRT1) Gene in Multiple Sclerosis

Objective: Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. Sirtuin 1 (SIRT1) is a neuroprotective enzyme in MS patients. The aim of our study was to investigate the relationship between a genetic variant of SIRT1 and MS. Design: Controlled prospective study Setting: Department of Neurology, Bulent Ecevit University Medical Faculty, Zonguldak, Turkey Subjects and Methods: We determined SIRT1 genotypes by polymerase chain reaction (PCR) and confronting two-pair primers (CTPP) methods in 93 MS patients and 100 healthy controls Intervention: For genetic analysis, 5 ml of venous blood was drawn from each patient into tubes containing EDTA Main Outcome Measures: SIRT1 gene polymorphisms and recorded expanded disability status scale (EDSS) for MS patients Results: We found a significant difference between the rs2273773 polymorphism of the SIRT1 gene of MS and the control group (p = 0.011). We also found an association between MS disease and the haplotypes of rs7895833, rs7069102 and rs2273773 polymorphisms. Conclusion: We have shown that rs2273773 polymorphism of the SIRT1 gene might be a risk factor for MS disease in the Turkish population. Also, additional studies are needed to clarify the role of the SIRT1 gene in the pathogenesis of MS disease