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Summary The autoinflammatory disorders differ in severity, as well as age of onset, duration, and manifestations, but they all share some common features: recurring fever peaks, inflammation of serosal membranes, musculoskeletal involvement, varying types of skin rash, amyloidosis as a sequel of the disease. TRAPS is very rare in Turkish population and we present two unrelated Turkish children with similar clinical phenotypes and laboratory findings related with autoinflammatory disorders and with novel p. Y331X mutation in TNFRSF1A gene. Both of the patients were male and they had recurrent fever without abdominal pain and arthralgia. Full cDNA and exon–intron binding regions of TNFRSF1A, MEFV, MVK, CIAS1 genes were analysed by direct DNA sequencing methods in order to differentiate TRAPS, FMF, HIDS, CINCA/MWS/FCAS respectively. We screened ten exons of TNFRSF1A gene, and detected a heterozygous c.1080C>G nucleotide substitution in exon 10 in both of the unrelated patients, resulting p.Y360X nonsense (protein truncated) mutation. According to classical TNFRSF1A gene nomenclature and the agreement of 30th amino acid as the first one, it is accepted as p.Y331X. It was interesting to determine same mutations in fathers of two patients. In one of the cases, E148Q heterozygous mutation, which is one of the disease-causing mutations of MEFV gene, was detected. No nucleotide substitution was identified in exon and exon–intron splicing regions encoding 396 amino acid of MVK gene in both of the patients. In CIAS1 gene, two different nucleotide substitutions resulting synonymous amino acid mutation were detected in exon 3: c.[732G>A] and c.[786A>G] nucleotide substitutions and compatible p.A242A (according to c.DNA p.A244A) and p.R260R (according to c.DNA p.R262R) synonymous amino acid mutations. These nucleotide substitutions were also detected in parents and were reported to be normal variations in Turkish population. In conclusion, in Turkish patients, with dominantly inherited recurrent fever, TRAPS is a diagnosis worthy of attention and novel mutations have to be reported with phenotype associations.

We aimed to evaluate the relationship between 174 promoter region of the interleukin-6 (IL-6) C/G gene polymorphism and high sensitive C-reactive protein (hs-CRP), fibrinogen and carotis intima-media thickness (CIMT), body mass index, homeostatic model assessment (HOMA) insulin resistance index, serum lipid parameters, in polycystic ovary syndrome (PCOS) patients carrying a potential risk for developing cardiovascular disease (CVD). We studied 88 PCOS patients and 119 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria. The genotype IL-6 distribution did differ between the control group (CC 10.1%, GC 63.0%, GG 29.6%) and the PCOS patients (CC 5.7%, GC 29.5%, GG 64.8%) (P0.001). The frequency of the polymorphic G allele was also no similar for the group with PCOS as for the control group with 79.5% and 58.4% respectively (P0.001). Both in PCOS patients and in control group, no statistically significant difference was determined between C/C, G/C and G/G, and blood cholesterol levels, triglyceride levels, high-density lipoprotein levels, low density lipoprotein levels, fasting blood sugar levels, insulin levels, HOMA values, CIMT measurements either on the right or left side, hs-CRP, f-testosterone, fibrinogen and 17 alpha-hydroxy-progesterone levels (P0.05). Gene polymorphism of IL-6 -174 GC is a risk factor for PCOS in Turkish patients, but we found no relationship between the cardiovascular risk factors and IL-6 -174 GC gene polymorphism in women with PCOS and healthy subjects. Our negative results in risk factors of CVD can probably be explained by the fact that metabolic parameters and endothelial systems of patients may not yet be affected in this short time of period.

Interleukin (IL)-10 is a major anti-inflammatory cytokine that has been associated with obesity and type 2 diabetes. We aimed to evaluate the IL-10 gene polymorphisms in polycystic ovary syndrome (PCOS) and control subjects. Ninety-one young women with PCOS and 74 healthy control women were included in our study. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin and IL-10 gene polymorphism genetic analysis and carotid intimae media thickness (CIMT) were measured. The genotype and allele frequencies showed similar ratios between both the control and the patient group. The AA and AG genotypes in IL-10 polymorphism seemed to be relatively high, but statistically no significant difference has been detected in GG genotype. Our results show that IL-10 gene polymorphism of PCOS patients has no effect on inflammatory markers, metabolic parameters (fasting insulin, fasting glucose, HOMA-IR), carotid intimae media thickness and Ferriman- Gallwey scoring. These data will be different in PCOS patients with different ethnical origin.

The aim of this study is to investigate Arg753Gln allele polymorphisms of toll-like receptor-2 (TLR2) gene distribution, allele frequency in urinary tract infection (UTI) and genotype-phenotype association of TLR2 gene in children with UTI. The polymorphism was investigated in 124 children with UTI (22 boys and 102 girls; mean age 5.81 +/- 3.47 years) with direct DNA sequencing-based method. TLR2 gene Arg753Gln allele frequency was higher in the patient group when compared with control group (OR 3.14, 95%CI 1.53-6.44, P < 0.001). The frequency of the Arg753Gln allele was significantly higher in gram-positive group than in gram-negative group (OR 7.64, 95%CI 2.80-20.81, P < 0.001). The frequency of UTI was found significantly higher in the Arg753Gln allele carriers of TLR2 gene than the non-carriers (OR 4.94, 95%CI 1.09-22.33, P < 0.05). Similarly, the incidence of asymptomatic UTI was also found significantly higher in the group carrying Arg753Gln allele (OR 3.73, 95%Cl 1.54-9.04, P < 0.05). As a result, we suggest that TLR2 gene could be the predisposing factor for urinary tract infection. Additionally, we observed that subjects carrying the TLR2 Arg753Gln allele had higher risk of urinary tract infection with gram-positive pathogens, history of more than two attacks of UTI and asymptomatic UTI.