Gene Expression Profiles of Tumor Necrosis Factor-α and Endothelin-1 in Obstructive Sleep Apnea.

BACKGROUND/AIMS: The aim of this study was to observe the relationship between the gene expression profiles of tumor necrosis factor (TNF)-α and endothelin (EDN)-1 and obstructive sleep apnea (OSA). METHODS: A prospective, cross-sectional study performed at a tertiary-care academic center; 108 patients with snoring and day-time sleeplessness were included in this study carried out in the Otolaryngology Department. All patients were evaluated with 1-night polysomnography (PSG). There were 63 patients with OSA and 45 patients without OSA. In the OSA group, the median apnea hypopnea index (AHI) was 29.1; in the non-OSA group, the median AHI was 2.1. Blood samples were obtained from all 108 patients for the genetic analysis of the expression of TNF-α and EDN-1. PSG findings and gene expression levels were evaluated in both groups. RESULTS: The median (range) age was 46 (20-81) years, BMI 24.9 (15-49), EDN-1 gene expression 0.45 (0.02-67.88) pg/µL, and TNF-α gene expression 1.71 (0.08-59.52) pg/µL. We found that EDN-1 and TNF-α gene expression levels were significantly higher in the OSA group than in the control group (p = 0.009 vs. p < 0.001). CONCLUSION: EDN-1 and TNF-α gene expression levels were associated with the occurrence of OSA.

Coffin-Siris syndrome with café-au-lait spots, obesity and hyperinsulinism caused by a mutation in the ARID1B gene.

Coffin-Siris syndrome (CSS) (MIM 135900) is characterized by developmental delay, severe speech impairment, distinctive facial features, hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum. Recently, it was shown that mutations in the ARID1B gene are the main cause of CSS, accounting for 76% of identified mutations. Here, we report a 15 year-old female patient who was admitted to our clinic with seizures, speech problems, dysmorphic features, bilaterally big, large thumb, café-au-lait (CAL) spots, obesity and hyperinsulinism. First, the patient was thought to have an association of neurofibromatosis and Rubinstein Taybi syndrome. Because of the large size of the NF1 gene for neurofibromatosis and CREBBP gene for Rubinstein Taybi syndrome, whole exome sequence analysis (WES) was conducted and a novel ARID1B mutation was identified. The proband WES test identified a novel heterozygous frameshift mutation c.3394_3395insTA in exon 13 of ARID1B (NM_017519.2) predicting a premature stop codon p.(Tyr1132Leufs*67). Sanger sequencing confirmed the heterozygous c.3394_3395insTA mutation in the proband and that it was not present in her parents indicating de novo mutation. Further investigation and new cases will help to understand this phenomenon better.

The role of Human Dectin-1 Y238X Gene Polymorphism in recurrent vulvovaginal candidiasis infections.

Recurrent vulvovaginal candidiasis (RVVC) is defined as having four or more symptomatic vulvovaginal candidiasis (VVC) attacks within a year. This study aimed to investigate whether Human Dectin-1 Y238X Gene Polymorphism plays a role in RVVC pathogenesis. In order to examine and explore this aim, an experimental study was undergone. The clinical study design was conducted with 50 women diagnosed with RVVC and had four or more symptomatic VVC attacks who were included in the experimental group; while 50 women who did not have previous RVVC history and diagnosis and did not have vaginal discharge and itching in the past year were included in the control group. Blood samples were collected from these patients and transferred to EDTA tubes, to investigate the Dectin-1 Y238X gene polymorphism, and stored at -80°. When Dectin-1 genotypes were compared, there was no significant difference between the two groups (p = 0.452, p = 0.615, p = 0.275). History of familial RVVC was significantly higher in the experimental group (p = 0.001). When the multivariate analysis was used to evaluate factors that could determine RVVC frequency, history of familial RVVC was found to increase the frequency of RVVC attacks by 3.3 units. This study is the first-of-its-kind to investigate the correlation between Dectin-1 Y238X polymorphism, which has not been previously studied in the Turkish population, and RVVC. The result of this study suggests that there is no correlation between this polymorphism and RVVC.

Detection of kinase amplifications in gastric adenocarcinomas.

AIM: To determine the incidences of copy number aberrations of receptor kinases and their relations in Turkish patients with gastric adenocarcinoma. MATERIALS AND METHODS: The prevalence of genomic copy number aberrations of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2)/topoisomerase IIa (TOP2A), centrosome-associated kinase aurora A (AURK A), centrosome-associated kinase aurora B (AURK B), and mesenchymal-epithelial transition factor (MET) genes and polysomies of related chromosomes were analyzed by fluorescent in situ hybridization (FISH) in tumor samples from 35 patients with gastric cancer. RESULTS: There were 28.6%, 65.7%, 20.0%, 17.1%, 60.0%, and 45.7% cases considered FISH-positive for EGFR, MET, HER2, TOP2A, AURK A, and AURK B genes, respectively. Statistically significant associations were determined in detection of amplifications of 1) EGFR gene with chromosome 7 polysomy, 2) MET gene in nonpolysomic chromosome 7 nuclei, 3) HER2/TOP2A genes in nonpolysomic chromosome 17 nuclei, 4) coamplification of HER2/TOP2A in poorly differentiated carcinomas, and 5) AURK A gene in nonpolysomic chromosome 20 nuclei. Most of the aberrations were predominantly seen in poorly differentiated tumors, but a high rate of the amplified MET gene was also detected in moderately differentiated carcinomas. CONCLUSION: Chromosome 7 polysomy may be responsible for EGFR gene amplifications, and we concluded that MET and AURK A genes amplifications were commonly seen aberrations in gastric adenocarcinomas and may offer information about disease progression and administration of individualized treatment for gastric cancer patients.

Detection of deletions and/or amplifications of genes related with lung cancer by multiplex ligation-dependent probe amplification (MLPA) technique.

BACKGROUND: Lung cancer has the leading mortality rate among all cancers and it is the second most common cause of death following cardiovascular diseases.The aim of the study was determining deleted and/or amplified regions of 64 different loci previously associated with lung cancer, by using Multiplex Ligation-dependent Probe Amplification (MLPA). RESULTS: The most frequently seen deletions in lung cancerous tissues were in 2p, 3p, 13q, 17p, 16p and the most frequently seen amplifications were in 17q, 8p and 5q. We observed same deletions in the same regions in normal lung tissues as in cancerous tissues in lower frequencies. Deletions in 5q, 8p, 9q, 10p, 11p. 11q, 12p, 14q, 17q and 21q probe regions were seen especially in cancerous tissues. MATERIALS/METHODS: One hundred non small cell lung cancer (NSCLC) tissue samples which had been previously examined histopathologically were included in this investigation. DNA extracts of normal lung tissues from the same patients were used as control group in the study. CONCLUSIONS: As a conclusion, it was determined that MLPA is an alternative technique which can give cheap, fast and reliable results in the screening of lung cancers. The findings obtained in the study are compatible with the literature. MLPA is one of the most important molecular techniques which have been developed recently and it can be used in cancer screening easily and reliably.