No Association between Polymorphisms of Vitamin D and Oxytocin Receptor Genes and Autistic Spectrum Disorder in a Sample of Turkish Children

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social skills and communication with repetitive behaviors. Etiology is still unclear although it is thought to develop with interaction of genes and environmental factors. Oxytocin has extensive effects on intrauterine brain development. Vitamin D, affects neural development and differentiation and contributes to the regulation of around 900 genes including oxytocin receptor gene. In the present study, the contribution of D vitamin receptor and oxytocin receptor gene polymorphisms in the development of ASD in Turkish community was investigated. To our knowledge, this is the first study examining these two associated genes together in the literature. Methods: Eighty-five patients diagnosed with ASD according to DSM-5 who were referred to outpatient clinics of Child and Adolescent Psychiatry of Baskent University and Mersin University and 52 healthy, age and gender-matched controls were included in the present study. Vitamin D receptor gene rs731236 (Taq1), rs2228570 (Fok1), rs1544410 (Bsm1), rs7975232 (Apa1) polymorphisms and oxytocin receptor gene rs1042778 and rs2268493 polymorphisms were investigated using real time polymerase chain reaction method. Results: No significant difference between groups in terms of distribution of genotype and alleles in each of polymorphisms for these genes could be found. Conclusion: Knowledge of genes and polymorphisms associated with the development of ASD may be beneficial for early diagnosis and future treatment. Further studies with larger populations are required to demonstrate molecular pathways which may play part in the development of ASD in Turkey

Comparative investigation of antitumoral effectiveness of Rho-kinase inhibitor Y-27632, pravastatin and atorvastatin in anaplastic thyroid cancer cell culture

Anaplastic thyroid cancer is an aggressive malignancy with a poor prognosis. In metastatic cases instead of treatment alternatives including surgery, radiotherapy, and chemotherapeutic regimens, targeted treatments should be sought for. Statins are 3-hidroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, and inhibit conversion of HMG-CoA into mevalonate. Inhibition of mevalonate pathway Ras prenylation, can also inhibit tumoral growth. Rho/Rho kinase pathway has an important role in tumoral proliferation, and metastasis in which activity of ROCK increases leading to tumoral invasion. Herein we investigated antitumoral effectiveness of two HMG-CoA reductase inhibitor statins namely pravastatin, and atorvastatin, and Rho-kinase inhibitor Y-27632 in anaplastic thyroid cancer cell cultures through suppression of cellular proliferation. Various concentrations of pravastatin (20, and 60 μM), and atorvastatin (10, and 30 μM), Y-27632 (10, and 30 μM), and their combinations including pravastatin -Y-27632 (20 μM + 10 μM; 60 μM + 30 μM), atorvastatin - Y-27632 (10 μM + 10 μM, and 30 μM + 30 μM) solutions were prepared. Anaplastic thyroid cancer cell culture media were treated with these more water-soluble drug solutions of pravastatin which induced lower dose-, and time-dependent decreases in cellular indices relative to more lipid-soluble atorvastatin which also markedly suppressed cellular proliferation. Y-27632 also decreased cell indices in a dose-, and time-dependent manner. Combination of Y-27632 with pravastatin, and atorvastatin did not demonstrate additive, synergic or antagonistic interactions. HMG-CoA reductase, and also Rho-kinase inhibitors are promising treatment alternatives of anaplastic thyroid cancers. Further in vivo, and clinical studies are needed on this issue

Lack of association polymorphisms of the IL1RN, IL1A, and IL1B genes with knee osteoarthritis in Turkish patients

Purpose: To examine whether polymorphisms of the interleukin 1 receptor antagonist (IL1RN), interleukin 1 alpha (IL1A) and interleukin 1 beta (IL1B) genes are markers of genetic susceptibility to knee osteoarthritis in Turkish patients. Methods: One hundred and seven patients with knee osteoarthritis and 67 controls were studied. Three polymorphisms of IL1A, IL1B, and IL1RN genes were typed from genomic DNA. Allelic frequencies were compared between patients and control subjects. Results: No significant differences were observed in genotype and allele frequencies of the IL1RN VNTR, IL1A+4845, IL1B+3953 genes polymorphisms between patients and controls. Furthermore, we did not detect any association genotypes of the polymorphisms with the clinical, radiological, and laboratory profiles of patients. Conclusions: The present study suggest that the IL1RN VNTR, IL1A+4845, IL1B+3953 genes polymorphisms are not genetic markers of susceptibility to knee osteoarthritis in Turkish patients, and are unrelated to the clinical, radiological, and laboratory characteristics of knee osteoarthritis