br Materials methods br Results FAS c AA

Materials & methods
Results FAS c.-671AA, AG and GG genotypes and A and G Ebastine australia frequencies were similar in both patients with FMF and healthy control groups, and no significant difference was found (P>0.05, Table 1). The frequency of TC genotype in FASLG in the healthy controls was significantly higher than the FMF patients (P=0,010). Although the CC genotype in the patients was higher than the control group but no significant difference was found (P=0.169). The frequencies of T and C alleles were %50 and %50 in the patient group and %49.30 and %50.70 in the control group, respectively and no statistically significant difference were found between the patients and the control groups (P=0.912, Table 1). As shown in Table 1, no significant difference was found between the patient and control groups in terms of haplotype frequencies (P>0,05). As shown in Table 2, no significant difference was found between clinical manifestations and FAS c.-671A>G, FASLG c.-844C>T polymorphisms (P>0,05).
Discussion Several studies have demonstrated that polymorphisms in the FAS and FASLG confer susceptibility or severity to other rheumatic disease such as rheumatoid arthritis (Yıldır et al., 2013, Kobak and Berdeli, 2012), systemic lupus erythematosus (Moudi et al., 2013, El Gendy et al., 2016). To the best of our knowledge, this is the first study in the medical literature concerning an association of the polymorphisms in the FAS and FASLG with FMF. Apoptosis is an important biological cycle that regulates physiological cell death in various tissues and cells of the organism, and helps to maintain the continuity of homeostasis (Hacker and Vaux, 1997, Zornig et al., 2001). The Fas molecule, known as CD95 or APO-1, is a cell surface receptor and provides apoptotic signaling in many cell types (Muschen et al., 2000). FasL (TNFS6 or CD95L), a member of the tumor necrosis factor superfamily, binds to its receptor (Fas) and initiates apoptosis cascade. The Fas-FasL signaling pathway is an important mechanism in the regulation of apoptosis. Disorders in the Fas-FasL system has an important role in inflammation, graft rejection, autoimmune diseases, and in some types of cancer (Lieber et al., 1976, Savill, 1994, Houston and O'Connell, 2004, Zhang et al., 2009a, Zhang et al., 2009b, Wang et al., 2012). It was reported that there is an association between functional FAS/FASLG polymorphic variants and cardiovascular diseases in the Chinese population (Xuan et al., 2015). Özen et al. showed that the expression of FAS and FASLG in the neutrophil membrane of FMF patients elevated and that neutrophil apoptosis increased in FMF patients at the time of acute attack (Ozen et al., 2001). In our study; in the FASLG c.-844TC genotype frequency was found to be significantly lower in the FMF patients than the healthy control group. Although not statistically significant, the frequency of FASLG c.-844CC genotype was higher in FMF patients than in control group. The c.-844C>T functional polymorphism in the promoter region of the FASLG is located in the binding region of the transcription factor CAAT/enhancer binding protein beta (C/EBPβ). Besides it was reported that T allele was reported to decrease transcription activity compared to C allele (Wu et al., 2003). It has been reported in the literature that c.-844C>T polymorphism should be considered as a potential marker in predicting clinical outcome of some tumor types (El-Hamamsy et al., 2016). The increase in FASLG expression can lead to malignant transformation and progression. Many studies reported that the c.-844C>T polymorphism in the FASLG or soluble FasL (sFasL) level is high in various types of cancer (Reimer et al., 2000, Mottolese et al., 2000, Munakata et al., 2000, Ito et al., 2000, Cao et al., 2010). Our findings suggests that although they did not reach a statistically significant level, higher frequencies of FASLG c.-844CC genotype in patients with FMF may be related to delayed apoptosis of neutrophils and ultimately cause neutrophilic inflammation by increasing FASLG expression.