Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease

Behcet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behcet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behcet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 x 10(-8)). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production

Genomic analysis reveals the biotechnological and industrial potential of levan producing halophilic extremophile, Halomonas smyrnensis AAD6T

WOS: 000359435700004PubMed ID: 26251777Halomonas smyrnensis AAD6T is a gram negative, aerobic, and moderately halophilic bacterium, and is known to produce high levels of levan with many potential uses in foods, feeds, cosmetics, pharmaceutical and chemical industries due to its outstanding properties. Here, the whole-genome analysis was performed to gain more insight about the biological mechanisms, and the whole-genome organization of the bacterium. Industrially crucial genes, including the levansucrase, were detected and the genome-scale metabolic model of H. smyrnensis AAD6T was reconstructed. The bacterium was found to have many potential applications in biotechnology not only being a levan producer, but also because of its capacity to produce Pel exopolysaccharide, polyhydroxyalkanoates, and osmoprotectants. The genomic information presented here will not only provide additional information to enhance our understanding of the genetic and metabolic network of halophilic bacteria, but also accelerate the research on systematical design of engineering strategies for biotechnology applications.Scientific and Technological Research Council of Turkey (TUBITAK) [MAG/110M613]; Marmara University Research Fund [FEN-C-YLP-060911-0280]This research has been financially supported by The Scientific and Technological Research Council of Turkey (TUBITAK) through Grant MAG/110M613 and by Marmara University Research Fund through Grant FEN-C-YLP-060911-0280

CEBPB transkripsiyon faktörünün MN1 ekspresyonu üzerindeki etkisi

Transkripsiyonel düzenleyici olarak rol oynayan yüksek MN1 gen ekspresyonunun in vivo fare modelinde myeloproliferatif hastalık (MPD) gelişimine, yüksek MN1 ekspresyonu birlikte CBFb-MYH11 varlığının ise akut miyeloid lösemi (AML) gelişimine neden olduğu gösterilmiştir. UCSC Genome Browser’da meningioma1 (MN1) bazal promoter bölgesini analiz ettiğimizde ENCODE projesi kapsamında Hela hücrelerinde ChIP dizileme ile CCAAT enhancer binding beta (CEBPB) transkripsiyon faktörüne ait bir peak saptanmıştır. Fakat CEBPB’nın bu bölgeye bağlandığı doğrulanmamış ve fonksiyonel önemi araştırılmamıştır. Bu çalışma ile CEBPB geninin MN1 ekspresyonu üzerindeki etkisinin araştırılması amaçlanmıştır.Yüksek seviyede MN1 eksprese eden servikal hücre soyu olan HeLa ve AML hücre soyu olan NB4 kullanıldı. CEBPB bu hücrelerde siRNA ile baskılanarak, 24., 36., 48., 72. ve 96. saatlerde MN1 ekspresyonu üzerinde değişikliğe neden olup olmadığı kantitatif gerçek zamanlı PCR yöntemiyle araştırıldı.24, 36, 48. saatlerde HeLa hücrelerinde CEBPB’ nin baskılanmasının MN1 ekspresyonu üzerinde etkisi olmadığını göstermiştir. 72. ve 96. saatte ise MN1 ekspresyonun 1,5 kat arttığı gösterilmiştir (Spearman korelasyon testi, p<0,01). NB4 hücrelerinde ise 48. saatte etkisi olmadığı ve 72. saatte 1,4 ve 96. saatte 1,3 kat arttığı göstermiştir (Spearman korelasyon testi, p<0,01).Bu sonuçlar CEBPB baskılanmasının MN1 ekspresyonu üzerinde geç ve düşük düzeyde etkisinin olduğunu göstermiştir. Elde ettiğimiz bu bulguların reporter deneyleri gibi daha ileri analizlerle doğrulanması gerekmektedir. Bu çalışma, CEBPB’nin indirekt olarak veya koregulator olabilecek başka faktörlerle kompleks oluşturup, MN1 transkripsiyonunu düzenleyebileceğini düşündürmektedir

TT polymorphism in rs2165241 and rs1048661 region in lysyl oxidase like-1 gene may have a role in stress urinary incontinence physiopathology

Aim: In experimental studies, lysyl oxidase like-1 (LOX-L1) (-/-) mice were shown to have similar pelvic floor dysfunction to female rats. LOX-L1 levels in endopelvic fascia decrease as a result of increasing births in women with pelvic prolapse. For these reasons, we investigated the LOX-L1 gene polymorphism, which has an important role in connective tissue and collagenous metabolism in stress urinary incontinence (SUI). Materials and Methods: A total of 87 women with SUI who underwent normal vaginal delivery and 87 controls were involved in the study. Single nucleotide gene polymorphisms in LOX-L1's rs1048661, G > T, pArg141Leu, Exon-1 SmaI; rs3825942, C > T, pGly153Asp, Hinf-1 and rs2165241, C > T, Intron-1 BsrI regions were searched. The results were statistically compared as alleles with 3 x 2 ?2-test. Results: A total of 32 (34%) GG, 20 (21%) GT, 42 (45%) TT, 32 (37%) GG, 43 (39%) GT, 21 (24%) TT polymorphisms in rs1048661; 30 (36%) CC, 16 (19%) CT, 37 (45%) TT, 41 (59%) CC, 15 (22%) CT, 13 (19%) TT polymorphisms in rs2165241; and 63 (72%) CC, 21 (24%) CT, 3 (4%) TT; 48 (6%) CC, 22 (30%) CT, 3 (4%) TT polymorphisms in rs3825942 were found in patients and the control group, respectively. In patients, the TT polymorphism in the rs1048661 and rs2165241 region were found to be significant. Conclusions: The homozygote TT polymorphism in the rs1048661 and rs2165241 region of LOX-L1 gene may be responsible from SUI physiopathology