Abstract Aim Functional polymorphisms located in FOXP 3 intron 1 was recently found to be associated with rheumatoid arthritis ( RA ). Although RA is an autoimmune disease, there is supporting evidence that activated maladaptive responses including pro‐inflammatory pathways play roles in osteoarthritis ( OA ), similar to RA . The aim of this study was to explore the relationship between rs2232365 (‐924A/G) and rs3761548 (‐3279A/C) polymorphisms as well as possible changes in the 600 bp promoter region of FOXP 3 and knee OA . Methods Patients with primary knee OA ( n = 300) and healthy individuals ( n = 300) were examined for rs3761548 and rs2232365 FOXP 3 gene polymorphisms by the polymerase chain reaction–restriction fragment‐length polymorphism method. The 600 bp promoter region (between −500 and +100) of the gene was also sequenced with direct sequencing in 50 knee OA patients and 50 healthy individuals. Results There were no sequence variants in the promoter region tested both in OA patients and healthy controls. The SNP rs2232365 showed no association with OA susceptibility and severity and the results of other genetic models were also nonsignificant. On the other hand, rs3761548 AC ( P = 0.003), AA + CC ( P = 0.0014) as well as AC + AA ( P = 0.40) genotypes showed association with Grade 4 knee OA patients. Conclusion Our findings indicated that the association between FOXP 3 rs2232365 polymorphism and knee OA tended to yield negative results but the FOXP 3 rs3761548 C allele was associated with elevated risk of OA in Grade 4 knee OA patients in a Turkish population.
Objective: In this study we aimed to find out whether FOXP3 promoter region -3499A/G polymorhism was associated with osteoarthiritis in a Turkish population. Method: The study group consists of 50 patients in 3rd stage and 100 patients in 4th stage osteoarthiritis and control group consists of 150 healthy individuals. FOXP3 genotypes were examined by PCR-RFLP method. Results: Our results show that there is no statisticially significant association between osteoarthiritis and FOXP3 -3499A/G polymorphism. The wild type AA genotype was 63%, polymorphic AG was 31% and GG was 6% in the control group, while they were 56%, 37% and 7% in the study group respectively. Conclusions: O steoarthiritis was seen higher in women than that of men in our study which is compatible with the results of previous results.
Cytosine (C-5)-specific DNA methyltransferases share a set of ten conserved motifs distributed evenly throughout the entire polypeptide chain. The first conserved motif contains a Phe, which is intimately associated with cofactor recognition. In the pseudo-DNA methyltransferase M.SpoI, encoded by the pmt1 gene in Schizosaccharomyces pombe, a Tyr replaces this Phe residue. We describe the properties of a mutant form of M.MspI, a typical cytosine (C-5)-specific DNA methyltransferase, in which Tyr replaces the conserved Phe. This mutant shows differences in ternary complex formation and in the pattern of covalent complex formation with an inhibitory, fluorinated DNA duplex which may be due to anomalous hydrogen bonding between the mutant Tyr hydroxyl group and the catalytic loop of the enzyme or through interference with cofactor binding.
Abstract Aim: To assess the association between human epoxide hydrolase exon 3 and 4 polymorphisms and pre‐eclampsia by carrying out a case‐control study in Turkish women. Methods: DNA was extracted from peripheral blood leukocytes, and genotype distribution of exon 3 and exon 4 of epoxide hydrolase gene ( EPHX ) was carried out in 271 patients and 155 controls. Results: There was no statistically significant difference in the distribution of genotypes between pre‐eclampsia without HELLP and pre‐eclampsia plus HELLP cases and controls for the exon 3 and 4 polymorphism of EPHX . However, we found a significant association between the predicted enzyme activity level and pre‐eclampsia ( P = 0.018). The distribution of subjects with predicted high, intermediate and low microsomal epoxide hydrolase enzyme (EPHX) activity were 23.2, 38.8 and 38% in cases and 12, 47.3 and 40.7% in controls, respectively. Conclusion: Although we could not find any association between genetic variability in exon 3 and 4 of EPHX and pre‐eclampsia, genetic variability in these two exons jointly modifies the predicted enzyme activity and may be a risk factor for pre‐eclampsia.
Preeclampsia (PE), which occurs in approximately 5% of pregnancies worldwide and constitutes clinically serious complications in 2–3%, is one of the leading causes of maternal and prenatal morbidity and mortality. Recent studies report that regulatory T (Treg) cells, which act as immunosuppressant, are associated with PE. It is clearly defined that FOXP3/Scurfin (Forkhead Box P3) is involved in the development and function of Tregs. However, there are different conclusions regarding the relationship between PE and FOXP3 gene polymorphisms for different populations. For this reason, in this study we investigate the association between FOXP3 gene promoter region polymorphisms and PE in a Turkish population 500 PE patients and 500 healthy pregnant women. Blood samples taken from pregnant women were studied by PCR-RFLP method. As a result, rs2232365 polymorphism was significantly associated with disease (p < .0001) while no significant association was found between rs3761548 polymorphism and the disease (p = .17). Based on these results, it is though that FOXP3 rs2232365 polymorphism may be predisposed to PE development in terms of Turkish population. However, further and functional studies are needed in terms of other polymorphisms and mutations.IMPACT STATEMENTWhat is already known on this subject? A number of recent publications suggest that Tregs may play a role in the pathogenesis of PE. It is known that a stable and high FOXP3 expression is required to maintain the suppressive T cell function of Tregs. Down regulation of FOXP3 in PE has been reported in many previous studies, but the mechanism is still uncertain.What do the results of this study add? Our study has examined two FOXP3 promoter region polymorphisms in terms of Turkish population for the first time. Rs2232365 polymorphism associated with the disease in heterozygous genotype.What are the implications of these findings for clinical practice and/or further research? It has been shown that FOXP3 gene promoter region polymorphisms may be associated with PE for Turkish population. Our results can be a guide for more detailed statistical evaluations and functional studies.
This study aimed to examine the leukotriene metabolism during COVID-19. In total, 180 participants were included in this study, of which 60 were healthy controls, 60 required intensive care units (ICU), and 60 did not require intensive care (non-ICU). The serum levels of 5-lipoxygenase (5-LO), 5-LO activating protein (ALOX5AP), and cysteinyl leukotriene (CYSLT) were measured, and the mRNA expression levels of 5-LO, ALOX5AP, and cysteinyl leukotriene receptor 1 (CYSLTR1) were investigated. Compared with the control group, both the non-ICU and ICU groups had lower levels of 5-LO and mRNA expression. ICU patients had lower levels of 5-LO and mRNA expression than non-ICU patients. CYSLTR1 mRNA expression was highest in the ICU group, followed by the non-ICU group, and healthy controls had the lowest mRNA expression levels. CYSLT levels were higher in the control group than in the non-ICU and ICU groups. CYSLTR1 expression was higher in patients than in controls; therefore, selective leukotriene receptor blockers can be used as treatment options. CYSLTR1 expression was higher in the ICU group than in the non-ICU group. Furthermore, CYSLTR1 mRNA expression may be a promising biomarker of COVID-19 severity.
Preeclampsia (PE), affecting 5-8% of pregnancies, is a common pregnancy disease that has harmful effects on mother and foetus. It has been found that the STOX1 (Storkhead Box 1), which is a transcription factor, carries variants associated with PE. Previous studies showed that, there was a strong relationship between PE and STOX1 variants. Therefore, we hypothesised that variants in the promoter region of the gene may be related to the onset of PE. The aim of this study is to investigate the contribution of STOX1 gene promoter region variants to PE. The blood samples taken from 118 PE patients and 96 healthy pregnant women were analysed by Sanger sequencing method. Sequence analysis results showed that, there is a-922 T > C polymorphism (rs884181) in the promoter region of the STOX1 gene. This polymorphism was found to be statistically significant in individuals with early onset PE (p = 0.02) and in PE (p = 0.014) compared to the control group.IMPACT STATEMENTWhat is already known on this subject? As a result of whole-exon studies on the STOX1 gene, polymorphisms were found to disrupt the structure/expression/function of the gene and strengthen its relationship with PE and HELLP syndrome. A previous study by our team found an association between Y153H, the most common polymorphism of STOX1, and early onset PE.What do the results of this study add? In our study, it was aimed to investigate the effect of genetic modifications in STOX1 gene promoter region on PE through the maternal genotype. Because any change in the promoter region affects the expression level of the gene. Also, for the first time, sequence analysis of the promoter region of STOX1 is investigated in PE. The variations in STOX1 appear to be important in PE especially in Early Onset PE.What are the implications of these findings for clinical practice and/or further research? Although PE is a disease that occurs with pregnancy and shows its effects most during this period, women and children with a history of PE are more prone to various disorders, especially cardiovascular diseases in the following years. Therefore, understanding the pathogenesis of the disease is important for both prevention and treatment process. Variations on STOX1 appear to be important in terms of disease risk.
