This study demonstrates that RANKL and osteoprotegerin expression are differentially regulated in various forms of periodontitis, and the relative RANKL/osteoprotegerin ratio appears to be indicative of disease occurrence. This information may confer diagnostic and therapeutic value in periodontitis.

The recently described family of toll-like receptors (TLRs) is a key player in host immunity by mediating inflammatory reactions against a wide range of pathogens. Mutations and polymorphisms in TLRs have revealed the importance of TLRs in human defence against diseases. TLR-2 is reported to interact with different bacterial structures, including lipoproteins, peptidoglycan and lipoteichoic acid. To assess the role of TLR-2 gene polymorphism in acute rheumatic fever (ARF) etiopathology, 61 independent Caucasian Turkish patients and 91 child and 116 adult controls were studied. Antistreptolycin O, C-reactive protein, sedimentation and white blood cell counts were studied to evaluate the clinical characteristics of the patients. Genomic DNA was extracted from peripheral blood using a standard column extraction technique. The Arg753Gln and Arg677Trp polymorphisms were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism. The PCR products for the TLR-2 gene were analysed on 1.5% agarose gel pre-stained with ethidium bromide. Compared with healthy adult controls, the Arg753Arg genotype was significantly decreased in the entire group of ARF cases [odds ratio (OR) 0.01, 95% confidence interval (95% CI) 0.0034-0.031, p<0.0001]. Significantly, ARF patients were just 16 times more frequent with Gln allele (OR 15.6, 95% CI 7.87-30.8, p<0.0001). Moreover, evidence for an intensifying effect of the Gln allele was noteworthy when patients with Arg753Gln genotype were compared with healthy controls (OR 97.1, 95% CI 32.5-290, p<0.0001). However, no Arg677Trp polymorphism was detected in either patients or controls. Our data suggest that there is strong evidence for the biological role of TLR-2 in ARF. The common TLR-2 Arg to Gln polymorphism at position 753 significantly contributes to the pathogenesis of ARF. These results will allow the construction of a profile of individuals prone to ARF and may assist in developing new therapies.

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.

The potential effects of macrophage migration inhibitory factor (MIF) on the natural immune response are due to the inhibition of immune cell activation, which is regulated by glucocorticoids. In this study, we investigated MIF -173G/C genotype and C allele frequency in 214 patients with idiopathic nephrotic syndrome (INS) and 103 healthy volunteers. We found significant increases in GC genotype (OR=3, p=0.0009) and C allele frequency (OR=2.5, p=0.0007) in INS. Upon classifying patients as steroid responsive (n=137) or resistant (n=77), a 20-fold over-expression of the CC-genotype was found in the steroid-resistant group (OR=20, p=0.0002). Moreover, a significant increase in C allele frequency in patients with focal segmental glomerulosclerosis (FSGS) has also been noted when compared with other histopathological groups (OR=3.2, p=0.0017). Furthermore, significant increases in the CC genotype (15.6% vs 3.3%) and C allele (75% vs 32%) frequencies have been found in patients with permanent renal function failure (p=0.013 and p=0.0002, respectively). Patients with the CC genotype were found to be at considerably increased risk of permanent renal failure (OR=5.43, p=0.013) and end-stage renal disease (OR=5.53, p=0.020). Additionally, there was a correlation between age of detection of proteinuria and CC genotype. We found an earlier age of onset of proteinuria in patients with the CC genotype (1.9+/-1.7 years) than in patients who were GC-heterozygous (3.7+/-3.1 years) and GG-homozygous (3.6+/-2.9 years, p=0.88). In summary, our results indicate that the MIF -173 C allele confers an increased risk of susceptibility to INS and plays a crucial role in glucocorticoid responsiveness.

The podocin (NPHS2) gene encodes podocin protein, which has an important role in glomerular ultrafiltration and controlling slit membrane permeability. The detection of an NPHS2 mutation affects the treatment plan for children with nephritic syndrome (NS). The frequency and spectrum of podocin mutations in the Turkish population have remained largely unknown. The aim of this study was to screen for podocin mutations in Turkish patients with steroid-resistant NS (SRNS) and to compare it with other published series. There were 295 children with SRNS, originating from Turkey, included in this study. Forty-one patients (13.8%) had familial NS and 254 patients (86.2%) had sporadic NS. Mutation analysis was performed in all eight exons of the NPHS2 gene with the direct DNA sequencing method. There were 53 different pathogenetic NPHS2 mutations detected, including 37 novel mutations. The mutation detection rate was 24.7% for all patients, 29.2% for familial, and 24% for sporadic SRNS. The most common mutated exon was exon 5 (52 allele). The presence of mutations in exon 4 was found to increase the risk of end-stage renal disease (ESRD). Among patients with mutations, the rates of renal failure and/or ESRD (26%) were significantly higher than in those without mutations (12.6%). The mean time of progression to renal failure and ESRD in patients with mutations (1.8 +/- 2.5 years) was significantly shorter than in patients without mutations (3.7 +/- 4.0 years). Additionally, in patients with heterozygote mutations, fewer cases (13.6%) progressed to renal failure and/or ESRD than in with patients who had homozygote/compound heterozygote mutations (31.3%). In conclusion, podocin mutations are responsible for some of both familial and sporadic SRNS cases in Turkey. The mutations in this gene should be searched for in every child after presentation with the first episode of NS.