To investigate the associations between Fas and FasL gene polymorphisms and susceptibility to knee osteoarthritis. Genomic DNA was obtained from 146 patients with knee osteoarthritis and 102 healthy controls. Genotype distributions and allelic frequencies of four polymorphisms of Fas (-670 G>A rs1800682, -1377 G>A rs2234767) and FasL (IVS2nt-124 A>G rs5030772, -844 T>C rs763110) genes were compared between the groups. Thereafter, this association was investigated between patients and controls of the same sex. There were significant differences between patients with knee osteoarthritis and controls regarding the genotype distributions and allelic frequencies of Fas-1377 G>A polymorphism (P = 0.0001 and P = 0.005, respectively). The Fas-1377 GG genotype and G allele were significantly more frequent in patients with knee osteoarthritis than in controls. Genotype distributions and allelic frequencies of Fas-670 G>A, FasL-844 T>C, and FasL IVS2nt-124 A>G polymorphisms did not differ between the groups (P > 0.05). However, there were no significant differences between patients and controls of the same sex (P > 0.05). These findings suggest that the Fas-1377 G>A polymorphism in the Fas gene related with apoptosis may contribute to susceptibility to knee osteoarthritis in the Turkish population. There is a need for further studies to evaluate the role of apoptosis in large cohorts.

To investigate associations of the Fas and FasL genes polymorphisms with rheumatoid arthritis (RA). One hundred patients with RA and age-, sex- and ethnically matched 101 controls were included. Four polymorphisms of Fas (-670 A>G rs1800682, -1377 G>A rs2234767) and FasL (IVS2nt-124 A>G rs5030772, -844 T>C rs763110) genes were typed from genomic DNA. Genotype distributions and allelic frequencies were compared between patients and control subjects. After the history and clinical examination of patients with RA, in terms of pain, fatigue and general health status were evaluated by visual analogue scale. Thereafter, erythrocyte sedimentation rate, C-reactive protein, blood count and rheumatoid factor levels were measured. The Disease Activity Score-28, Health Assessment Questionnaire and modified Sharp score were used to evaluate the disease activity, functional disability and radiological damage, and their relationships with the Fas and FasL gene polymorphisms were investigated. In patients with RA, CT and TT genotypes of FasL-844, polymorphism were twofold and 4.8-fold higher, and AA genotype of FasL IVS2nt-124 polymorphism was 3.4-fold higher than the control group (respectively, p = 0.05, p = 0.002, p = 0.039). T allele of FasL-844 polymorphism was more frequent in patients than controls (respectively, 52.5 vs. 41.4 %, p = 0.027). Any association was not detected between Fas (-670 A>G, -1377 G>A) and FasL (-844 T>C, IVS2nt-124 A>G) gene polymorphisms with the disease activity scores, functional disability and radiological damage. However, the Fas-670 A>G polymorphism was associated with drug therapy (p = 0.049). The distribution of GG genotype was higher compared to GA or AA genotypes in patients using triple disease-modifying antirheumatic drug therapy (71.4, 14.3 and 14.3 %, respectively). These findings suggest that the -844 T>C and IVS2nt-124 A>G polymorphisms in the FasL gene related with apoptosis may increase genetic susceptibility to RA in a Turkish population. In addition, the Fas-670 A>G gene polymorphism may be associated with disease progression. There is a need for further studies to clarify the genetic role of apoptosis in RA.

IntroductionCatalase (CAT), an antioxidant enzyme, catalyzes conversion of hydrogen peroxide to water and molecular oxygen, protecting cells against oxidative stress. The aim of this study was to investigate the possible association between CAT C262T polymorphism in the promoter region of the CAT gene and leukemia risk and to determine the relationship between CAT genotypes and CAT enzyme activities.Material and methodsGenotypes of 102 cases and 112 healthy controls’ genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism methods. Catalase activity was measured with the method of Aebi.ResultsThe frequencies of the T allele among the cases and controls were 28.4% and 25.9%, respectively (p = 0.75). The frequencies of CC, CT, and TT among cases were 57.8%, 27.4%, and 14.7%, respectively, while in controls, the frequencies of CC, CT, and TT were 54.4%, 39.3%, and 6.3%, respectively, which were not significantly different. Although CAT enzyme activity was lower in leukemia patients with TT genotypes than in controls, this did not reach statistical significance (p = 0.37).ConclusionsThis is the first report showing that CAT C262T polymorphism is not a genetic predisposing factor for the risk of leukemia in the Turkish population. However, additional research is needed to confirm these findings.

Pharmacogenomics harnesses the utility of a patient's genome (n = 1) in decisions on which therapeutic drugs and in what amounts should be administered. Often, patients with shared ancestry present with comparable genetic profiles that predict drug response. However, populations are not static, thus, often, population mobility through migration, especially enmasse as is seen for refugees, changes the pharmacogenetic profiles of resultant populations and therefore observed responses to commonly used therapeutic drugs. For example, in the aftermath of the Syrian civil war since 2011, millions have fled their homes to neighboring countries in the Middle East. The growing permanence of refugees and mass migrations is a call to shift our focus in the life sciences community from old models of pharmaceutical innovation. These seismic social changes demand faster decisions for "population-to-population bridging," whereby novel drugs developed in or for particular regions/countries can meet with rational regulatory decisions/approval in world regions impacted by migrant/refugee populations whose profiles are dynamic, such as in the Eastern Mediterranean region at present. Thus, it is important to characterize and report on the prevalence of pharmacogenes that affect commonly used medications and predict if population changes may call for attention to particular differences that may impact health of patients. Thus, we report here on four single-nucleotide polymorphism (SNP) variations in CYP2C9 and CYP2C19 genes among Mersin-Turkish healthy volunteers in the Mersin Province in the Eastern Mediterranean region that is currently hosting a vast number of migrant populations from Syria. Both CYP2C9 and CYP2C19 are very important pharmacogene molecular targets. We compare and report here on the observed SNP genetic variation in our sample with data on 12 world populations from dbSNP and discuss the feasibility of forecasting the pharmacokinetics of drugs utilized by migrant communities in Mersin and the Eastern Mediterranean region. This study can serve as a catalyst to invest in research in Syrian populations currently living in the Eastern Mediterranean. The findings have salience for rapid and rational regulatory decision-making for worldwide precision medicine and, specifically, "pharmacogenovigilance-guided bridging of pharmacokinetics" across world populations in the current era of planetary scale migration.

Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. Like other atopic diseases, asthma is a complex disorder caused by interactions between multiple genes of small to modest effect and equally important environmental factors. The aim of this study was to determine the TNF-α-308 g/a polymorphism and the TRAIL polymorphisms, and their influence on asthma in asthmatic patients and healthy subjects.