NPHS2 gene sequencing results in children of the Azerbaijani population with different types of nephrotic syndrome caused by chronic glomerulonephritis.

OBJECTIVES: The aim of the study was to determine the mutation of the podocin gene (NPHS2) in children with minimal changes diseases (steroid sensitive nephrotic syndrome (NS)) and steroid resistant NS. BACKGROUND: Despite the fact that the role of genetic factors is a well-known phenomenon, in NS there are still unknown aspects that are yet to be discovered. NS, type 2 is caused by NPHS2 gene and is characterised with proteinuria, minimal change disease on renal biopsy, poor response to steroid treatment, etc.METHODS: Twenty-nine children (65.5 % male, 34.5 % female) with nephrotic syndrome caused by chronic glomerulonephritis were examined and patients were tested for NPHS2 gene with Sanger technique. RESULTS: The average age was 7.2 ± 2.65 years. 82.8 % of patients had NS with minimal changes, 17.2 % had a steroid resistant NS. The analysis of the NPHS2 gene revealed a likely pathogenic (Arg168His), uncertain significance (Pro20Ley, Leu169Pro, Val180Met, Arg229Gln, Val290Met) and benign (Gly34Gly, Ala318Ala) variants. No novel variants were detected. CONCLUSION: This is the first study investigating the nephrotic syndrome related to NPHS2 gene in Azerbaijani population. The high prevalence of uncertain significance variants emphasises the importance of population studies in this region as such data are necessary for classifications of the detected genetic variants (Tab. 1, Ref. 25).

Fas/FasL gene polymorphism in patients with Hashimoto's thyroiditis in Turkish population.

OBJECTIVE: Hashimoto's disease is a polygenic disorder with complex etiopathogenesis. Apoptosis is proposed as one of its mechanisms. The Fas/Fas ligand cascade represents a major pathway initiating apoptosis. This study aims to evaluate the influence of Fas and FasL gene polymorphism in Hashimoto's thyroiditis in Turkish population. MATERIALS AND METHODS: A total of 112 patients with Hashimoto's thyroiditis and 112 cases of healthy control people were included in this study. The evaluation of genotype for Fas -670 A/G and FasL 843 C/T gene polymorphism was performed by using PCR-RFLP method. RESULTS: The FAS genotype and gene allele frequency distribution did differ between the control group (AA 36.6 %, AG 50.0 %, GG 13.4 %, A 61.6 %, G 38.4 %) and the Hashimoto's thyroiditis patients (AA 21.4 %, AG 50.9 %, GG 27.7 %, A 46.9 %, G 53.1 %) (p < 0.01). The evaluation of FasL genotype and gene allele frequency did not show statistically significant difference between the patient group (CC 27.7 %, CT 45.5 %, TT 26.8 %, C 50.4 %, T 49.6 %) and control group (CC 33.9 %, CT 44.6 %, TT 21,4 %, C 56.3 %, T 43.8 %) (p > 0.05). CONCLUSIONS: Gene polymorphism of Fas and G allele frequency may play a role in the regulation of apoptosis in thyroid autoimmune disorders. There is a need for further studies to clarify the genetic role of apoptosis in HT.

Prevalence and significance of MEFV gene mutations in patients with sarcoidosis.

OBJECTIVES: Sarcoidosis is a chronic granulomatous disease. Pyrin has anti-inflammatory activity in the regulation of inflammasomes and is encoded by the Mediterranean fever (MEFV) gene. MEFV gene mutations trigger the inflammatory cascade and cause familial Mediterranean fever (FMF). A relationship between various rheumatic diseases and MEFV gene mutations has been demonstrated. The aim of this study was to determine the prevalence of the MEFV gene mutation in Turkish patients with sarcoidosis and to detect any possible correlation with disease phenotype. METHOD: The study included 78 sarcoidosis patients and 85 healthy subjects matched for age, gender, and ethnicity. MEFV gene mutations were investigated with the FMF strip assay, which is based on reverse hybridization of biotinylated polymerase chain reaction (PCR) products. RESULTS: Of the 78 patients with sarcoidosis, nine (11.5%) were found to be carriers of MEFV gene mutations. The distribution of these nine mutations were: three (3.8%) V726A, two (2.5%) E148Q, two (2.5%) M680I, one (1.3%) A744S, and one (1.3%) K695R. Carriers of M694V, M694I, R761H, and P369S were not detected in any of the sarcoidosis patients. None of the sarcoidosis patients were found to be compound heterozygous carriers. The prevalence of the MEFV gene mutation carrier detected in the healthy control group was 22.4%. The distribution of the 19 MEFV gene mutations found in the healthy controls was: nine (10.6%) E148Q, two (2.3%) M694V, one (1.2%) M694I, one (1.2%) M680I, two (2.3%) V726A, one (1.2%) A744S, two (2.3%) K695R, and one (1.2%) P369S. When compared with the control group, a lower prevalence of the MEFV gene mutation carrier was found in sarcoidosis patients but this was not statistically significant (p = 0.067). In nine patients found to be MEFV gene mutation carriers, higher serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels and higher numbers patients with arthritis, enthesitis, and ankle arthritis were found (p = 0.01, p = 0.04, p = 0.028, p = 0.05, p = 0.05, respectively). CONCLUSIONS: When we compared Turkish sarcoidosis patients with the healthy control group, we found a lower prevalence of MEFV gene mutations. In sarcoidosis patients, the MEFV gene mutation carrier was found to be related to high acute-phase responses, arthritis, and enthesitis. The existence of MEFV gene mutations may have a preventive role with regard to the development of sarcoidosis. Prospective studies that include larger patient populations are needed.

Novel non-synonymous polymorphisms in the COX-1 gene in Turkish pediatric patients with cardiovascular anomalies.

Variation in the gene encoding cyclooxygenase-1 (COX-1) is involved in the process of aspirin resistance. This study investigated the genetic variations in the COX-1 gene. The 4 coding regions of the human COX-1 gene in 90 pediatric patients (median age of 6.5 months, 55% males) with cardiovascular anomalies were screened using DNA sequencing. Twenty coding-region variants causing amino acid substitutions as well as 2 new non-synonymous polymorphisms were identified. All variants were compared with an independent Caucasian population (N = 24 unrelated individuals). Most of the discovered polymorphisms were rare, although some variants resulted in amino acid changes occurring at a frequency >5% (W8R, P17L, Q41Q, Q240Q, D189E, and P188P). In addition, 2 new non-synonymous polymorphisms (F200L and D189E) were identified. These findings demonstrated novel genetic variants of the human COX- 1 gene. Future studies characterizing the functional impact of these variants are warranted.

Apoptosis-associated speck-like protein containing a CARD (ASC) expression profiles in familial Mediterranean fever (FMF) patients with different MEFV mutation patterns.

OBJECTIVES: The inflammasome complex and the inflammatory pathway have been implicated in the pathogenesis of the most common autoinflammatory disorder, familial Mediterranean fever (FMF). Pyrin, the protein product of the FMF gene MEFV, interacts with the inflammasome complex adaptor protein ASC/PYCARD (apoptosis-associated speck-like protein with a CARD). Pyrin and ASC can both function as either inducers or suppressors of the cellular inflammatory response. We aimed to characterize ASC-induced gene expression profiles in FMF patients with different MEFV mutation patterns. METHODS: A total of 165 Caucasian patients with clinical and molecular FMF diagnoses were enrolled in the study. ASC gene expression was quantified by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: ASC mRNA expression was increased in the MEFV mutation-positive group compared to the mutation-negative group (p = 0.001). The fold changes of ASC expression in the M694V homozygous (p = 0.02), M694V heterozygous (p = 0.012), compound heterozygous (p = 0.002), and R202Q/P369S/R408Q (p = 0.00) groups relative to the MEFV mutation-negative group were +2.4, +2.7, +3, and +3.4, respectively. qRT-PCR did not reveal a significant difference in ASC mRNA expression levels among the MEFV mutation-positive groups (p > 0.05). CONCLUSION: ASC mRNA expression was up-regulated in patients carrying MEFV mutations independent of mutation type. There was no significant relationship between specific MEFV genotypes and the level of ASC expression in the patient group analysed. Thus, the findings of this work may suggest a crucial relationship between mutant MEFV/pyrin and remarkable ASC up-regulation in FMF inflammation.

TLR2 and TLR4 gene polymorphisms in Turkish vitiligo patients.

BACKGROUND: It has been shown that toll like receptors (TLR) may be involved in some inflammatory skin diseases such as psoriasis, atopic dermatitis. Vitiligo is an acquired pigmentation disorder of unknown aetiology. A number of genes playing a role in inflammatory response may be associated with development of vitiligo. OBJECTIVES: To investigate whether there is an association between TLR 2 and TLR4 gene polymorphisms in Turkish patients with vitiligo. METHODS: A total of 100 patients (59 women and 41 men) with vitiligo and 100 controls (58 women and 42 men) were included in the study. The TLR2 gene Arg753Gln and TLR4 gene Asp299Gly and Thr399Ile polymorphisms were genotyped by using polymerase chain reaction and restriction fragment length polymorphism method. The data were analysed by Mann-Whitney U-test, chi-squared test and logistic regression analysis. RESULTS: Significant difference was found in the distribution of TLR2 Arg753Gln genotype and in the allele frequencies TLR2 753Gln between vitiligo patients and healthy subjects (P < 0.05). The distribution of TLR4 Asp299Gly genotype was significantly higher in the patient group (10%) than in the control group (%2) (P < 0.05). The TLR4 Thr399Ile distribution did not show any difference in both vitiligo and healthy groups. CONCLUSIONS: Our findings suggest that Toll-like receptor 2 gene Arg753Gln and Toll-like receptor 4 Asp299Gly gene polymorphisms are associated with vitiligo susceptibility in Turkish patients.

Fas/FasL promoter gene polymorphism in patients with rheumatoid arthritis.

OBJECTIVES: Fas/FasL is significantly involved in the pathogenesis of rheumatoid arthritis (RA). Fas/FasL gene polymorphism may be associated with susceptibility to rheumatoid arthritis and disease severity. AIM: To investigate the Fas 670 G/A and FasL 843 C/T genotype and allele frequency in patients with RA, and determine its potential association with susceptibility to the disease and the clinical parameters. METHODS: One hundred and one patients with RA and 105 healthy control subjects were enrolled in the study. Fas 670 A/G and FasL 843C/T genotype polymorphism was investigated by PCR-RFLP. Chi-square test was used for determining the genotype distribution and the allele incidence. RESULTS: There was no statistically significant difference between the patients with RA and the healthy subjects with respect to Fas-670 A/G and FasL-843C/T genotype distribution and allele frequency (P>0.05). While there was no statistically significant difference in disease severity and various clinical parameters, a correlation was detected between Fas-670 polymorphism and anti-CCP antibody and anemia (P<0.01 and P<0.03, respectively). CONCLUSIONS: Fas-670A/G and FasL-843C/T promoter gene polymorphisms are not considered to represent a major genetic risk factor for RA susceptibility and disease severity. However, based on these results, Fas-670 promoter polymorphism may modulate anti-CCP antibody synthesis and response in patients with rheumatoid arthritis.

Trimethylaminuria (fish malodour syndrome) in chronic renal failure.

Trimethylaminuria (fish malodour syndrome) is a rare genetic metabolic disorder presented with a body odour which smells like a decaying fish. This odour is highly objectionable, that can be destructive for the social, and work life of the patient. Trimethylamine is derived from the intestinal bacterial degradation of foods that are rich of choline and carnitine. Trimethylamine is normally oxidised by the liver to odourless trimethylamine N-oxide which is excreted in the urine, so, uremia may worsen the condition. Uremia itself may cause more or less unpleasant odour. Poor uremic control may worsen the odour. We reported this case because Trimethylaminuria is not usually considered in the differential diagnosis of malodour in chronic renal failure and it is the first case that shown the association with Trimethylaminuria and chronic renal failure in the literature.

Genetic factors that influence short-term neurodevelopmental outcome in term hypoxic-ischaemic encephalopathic neonates.

It is difficult to predict outcome in neonates that experience perinatal hypoxic ischaemia. Morbidity and mortality may be affected by genetic factors that augment inflammatory and coagulative responses. This prospective study analysed the effects of proinflammatory cytokine gene polymorphisms (tumour necrosis factor-α [TNFA] 308G>A and interleukin-6 [IL6] 174G>C) and prothrombotic factor gene mutations (prothrombin G20210A, factor V Leiden G1691A and methylenetetra hydrofolate reductase [MTHFR] C677T) on the early neurological prognosis in 40 term hypoxic ischaemic encephalopathic neonates. There were significant relationships for Sarnat and Sarnat staging with electroencephalographic findings, transfontanelle ultrasound (US) results, early neonatal outcome and neurological morbidity. Genetic mutations in the prothrombotic proteins, the TNFA 308G>A polymorphism and the cerebrospinal fluid levels of TNF-α protein were not related to clinical stage, electroencephalography, transfontanelle US or neurological status at discharge or at postnatal months 6 and 12. The IL6 174GC genotype demonstrated a protective role, being significantly correlated with normal electroencephalography, transfontanelle US and normal neurological findings at discharge. In conclusion, the IL6 174GC gene polymorphism seems to play a role in determining the risk and/or severity of perinatal cerebral injury.

Antimicrobial peptide hCAP-18/LL-37 protein and mRNA expressions in different periodontal diseases.

OBJECTIVE: To investigate the levels of antimicrobial peptide hCAP-18/LL-37 protein and mRNA expression in gingival tissues with different periodontal disease. MATERIALS AND METHODS: Ten patients with generalized aggressive periodontitis, 10 patients with chronic periodontitis, and 10 healthy controls were included in this study. Periodontal parameters including probing depth, clinical attachment level, plaque index, and papilla bleeding index were assessed in study subjects. hCAP-18/LL-37 mRNA analysis by RT-PCR and immunohistochemistry were performed in 19 samples provided enough RNA in terms of concentration and integrity. RESULTS: This study demonstrated that hCAP-18/LL-37 was a product of neutrophils. Tissue samples of chronic periodontitis patients had significantly higher immunostaining of hCAP-18/LL-37 on neutrophils infiltrating in both epithelium and connective tissue compared with controls. hCAP-18/LL-37 mRNA expression levels in tissue samples of chronic periodontitis patients seemed to be upregulated compared with controls. While two generalized aggressive periodontitis patients showed downregulated hCAP-18/LL-37 mRNA expression levels, one generalized aggressive periodontitis patient showed slightly increased hCAP-18/LL-37 mRNA level compared with controls. CONCLUSIONS: hCAP-18/LL-37 has an important role in innate response during periodontal inflammation. Local deficiency in hCAP-18/LL-37 might be a confounding effect in the pathogenesis of generalized aggressive periodontitis.

Monocyte chemoattractant protein-1 (MCP-1) 2518G/A gene polymorphism in Turkish type 2 diabetes patients with nephropathy.

Tissue macrophage accumulation is thought to induce insulin resistance during obesity and stimulate the progression of diabetic nephropathy (DN). The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene polymorphism in the healthy and patients with and without DN. The MCP-1 genotypes were determined in 43 patients with nephropathy and 43 without nephropathy and a control group of 105 healthy individuals. The genotype MCP-1 (-2518G/A) distribution did differ between the control group and the type 2 diabetic patients (P = 0.004). The frequency of the polymorphic G allele was also no similar for the group with type 2 diabetes as for the control group with 20.9 and 32.4%, respectively (P = 0.012). The AA genotype and A allele at MCP-1 -2518 was an independent risk factor for the progression of type 2 diabetes. In conclusion, MCP-1 AA genotype and A allele may play a specific role(s) in determining diabetic susceptibility, but do not seem to be important in the clinical manifestations of DN.

A novel Y331X nonsense mutation in TNFRSF1A gene in two unrelated Turkish families with periodic fever syndrome.

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.

Endothelial nitric oxide synthase (eNOS) gene polymorphism in early term chronic allograft nephropathy.

Chronic allograft nephropathy (CAN) is a complex phenomenon caused by underlying kidney disease with superimposed enviromental and genetic factors. CAN development begins with progressive renal microvascular injury. Endothelial cells play key roles in the regulation of vascular tone, permeability, and remodeling. A reduction in basal nitric oxide (NO) release as a result of genetic variation in endothelial NO synthase (eNOS) function may predispose to hypertension, thrombosis, vasospasm, and atherosclerosis, all contributing to the development of CAN. We analyzed the G894T mutation at exon 7 of the eNOS gene in relationship to CAN among 81 children with renal transplantations. The 20 patients who developed CAN underwent renal biopsies for histological confirmation. Proteinuria and hypertension were observed in CAN. We selected 173 healthy reference subjects. The G894T polymorphism of the eNOS gene was determined by PCR-restriction fragment-length polymorphism analysis. The group included 33 male and 48 female subjects who received 32 living-related grafts and 49 from deceased donors (DD) donors. Donor age (y) was 32.7 +/- 13.7 and the HLA A,B,DR mismatch number of the cadaveric cases was 3.5 +/- 0.79. The distribution of the genotypes were ENOS GG/GT/TT 48%, 33%, 19%, respectively. G-alleles frequency was 64.8%; T-allele frequency was 35.2%. ENOS G894T gene polymorphism did not seem to influence long-term renal allograft outcome. Recipient ENOS G894T gene polymorphism did not alter the risk of chronic allograft failure. Even if NO synthesis and bioactivity are influenced by this polymorphism, many vasoactive factors may have roles to suppress the advantageous effects of NO.

An inherited nonsense R1645X mutation in neuronal sodium channel alpha1-subunit gene in a Turkish patient with severe myoclonic epilepsy of infancy.

Severe myoclonic epilepsy of infancy (SMEI) is a well-known catastrophic epileptic syndrome. Several mutations of the sodium channel alpha 1 subunit (SCN1A ) gene were reported in patients with SMEI. Most of the mutations were DE NOVO. Inherited truncating mutations are very rare. Here a patient with a new nonsense mutation (c.4933 C>T; p.R1645X) of the gene is described. This mutation was inherited from the father who had only febrile seizures during childhood.

The relationship of the interleukin-6 -174 G>C gene polymorphism with cardiovascular risk factors in Turkish polycystic ovary syndrome patients.

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%) (P < 0.001). 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 (P < 0.001). 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 (P > 0.05). Gene polymorphism of IL-6 -174 G>C is a risk factor for PCOS in Turkish patients, but we found no relationship between the cardiovascular risk factors and IL-6 -174 G>C 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.

The relation of adiponectin and tumor necrosis factor alpha levels between endothelial nitric oxide synthase, angiotensin-converting enzyme, transforming growth factor beta, and tumor necrosis factor alpha gene polymorphism in adrenal incidentalomas.

OBJECTIVE: The aim of our study was to demonstrate demographic characteristics, presence of inflammatory markers, distribution of angiotensin-converting enzyme (ACE), tumor necrosis factor (TNF), endothelial nitric oxide synthase (eNOS) genotypes and relations among these parameters in these patients and control subjects. RESEARCH DESIGN AND METHODS: Study samples were collected from 50 patients with adrenal mass and 30 control groups. The eNOS, ACE, TNF-alpha, transforming growth factor (TGF)-beta genes polymorphisms, TNF-alpha, adiponectin levels were analysed in 50 unrelated Turkish patients with a diagnosis of adrenal incidentaloma (AI). RESULTS: There was statistically significant difference between TNF-alpha levels of patient and controls (p=0.048). We have not detected the connection between TGF-beta, TNF-alpha, ACE, eNOS gene polymorphism with serum TNF-alpha and adiponectin levels. In this study, we demonstrated that there were significant differences for ACE genotypes in the patients when compared to the controls (p<0.05). The percentages of the ID, DD, II genotypes for ACE gene polymorphism in the patients group were 30.0, 13.0, 7.0%, respectively. CONCLUSIONS: According to different cases of eNOS, TGF-beta, ACE, and TNF-alpha gene genotypes; no statistical significant difference was found between basal cortisol, ACTH, DHEAS, metanephrine, renin, aldosterone, normetanephrine, 17-hydroxyprogesterone, 1 mg low-dose dexamethasone suppression test-cortisol response and AI size. In this study, I/D genotype was determined to be statistically higher in ACE gene in patients with AI (p=0.014).

The (-174) G/C polymorphism in the interleukin-6 gene is associated with risk of papillary thyroid carcinoma in Turkish patients.

INTRODUCTION: Interleukins and cytokines play an important role in the pathogenesis of many cancers.We aimed to evaluate the interleukin (IL)-6 gene polymorphisms in patients with papillary thyroid carcinoma (PTC) and control subjects. MATERIAL AND METHODS: In this study, 42 patients with PTC and 340 healthy controls were included. Peripheral blood samples were taken from control group and patients, and blood samples were preserved at -80 C in tubes containing Na-EDTA. RESULTS: We also found a statistically significant difference between patients with PTC and the control group with respect to IL-6 genotype (p<0.05). IL-6 gene polymorphism in patients with PTC patients did not reveal statistically significant difference between the 2 groups (size of tumor >1 cm and <1 cm), multicentricity, RET-PTC types and capsule invasion (p>0.05).We also did not find a statistically significant difference between patients with PTC and the control group with respect to IL-6-gene allele frequency (p>0.05). DISCUSSION: Our data suggest that the IL-6 G-174 C polymorphism could play a role in thyroid cancer risk, but there is no effective role as a prognostic factor.

Association between Toll-like receptors 4 and 2 gene polymorphisms with chronic allograft nephropathy in Turkish children.

Toll-like receptor (TLR) gene polymorphism is known to impair intracellular signaling pathways following adaptive immune responses. Our aim was to investigate the distribution of TLR4 and TLR2 gene polymorphisms among pediatric renal transplantation patients in relation to chronic allograft nephropathy (CAN). In addition to 115 healthy controls, we included 69 renal recipients, 19 of whom were identified as CAN by biopsy scored according to the Banff criteria. Polymorphisms at TLR4 Asp299Gly and/or Thr399Ile were present in 11.6% of renal transplant recipients. None of these subjects was identified in cosegregation with the Thr399Ile allele, whereas three had an isolated Asp299Gly and five had an isolated Thr399Ile. Neither renal recipients nor healthy controls were homozygous for both Asp299Gly and Thr399Ile polymorphisms. However, TLR4 Thr399Ile polymorphism and Ile allele was greater among CAN (-) versus CAN (+) recipients (P > .05). The frequency of TLR2 mutant type Gln allele was significantly higher in recipients than among healthy controls (P < .0001). However, the Gln allele frequency was similar between CAN (+) and CAN (-) patients. The results of present study may be speculated to show TLR4 and TLR2 gene polymorphisms as protective factors from CAN development due to impaired immune responses.

FcgammaRIIa, IIIa and IIIb gene polymorphisms in Behçet's disease: do they have any clinical implications?

OBJECTIVE: Behçet's disease (BD) is a unique systemic vasculitis involving both arteries and veins of all sizes. Since Fcgamma receptors (FcgammaR) are important in mediating various immune effector functions, FcgammaR gene polymorphisms may affect the susceptibility to systemic inflammatory diseases such as BD. The aim of this study was to show the distribution of FcgammaRIIa, IIIa ve IIIb receptor gene polymorphisms in BD, and to investigate possible genotype-phenotype relationships. METHODS: In this cross-sectional study, FcgammaRIIa (H/H131, H/R131, R/R131), IIIa (F/F158, F/V158, V/V158), and IIIb (NA1/NA1, NA1/NA2, and NA2/NA2) receptor gene polymorphisms were investigated in 216 unrelated Turkish BD patients (M/F: 130/86) and in 241 healthy subjects, using an allele-specific polymerase chain reaction. RESULTS: The FcgammaRIIa R/R131 (p=0.019) and FcgammaRIIIa F/F158 genotypes (p=0.001) were found to be significantly more frequent in BD compared with healthy controls, whereas the FcgammaRIIIb genotypes were not (p=0.108). Allele analysis showed that the FcgammaRIIIa 158 (p=0.001) and FcgammaRIIIb NA2 (p=0.016) alleles were more frequent in BD than in healthy controls. In BD patients the FcgammaRIIIa V/V158 genotype was significantly associated with the presence of arthritis (p=0.002) and with an earlier disease onset (p=0.008), while the FcgammaRIIIb NA2/NA2 genotype was significantly associated with disease severity (p=0.02), vascular involvement (p=0.014), and pathergy positivity (p=0.02). CONCLUSION: We found that the genotype frequencies and allelic distributions of the FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb gene polymorphisms were significantly different between BD patients and healthy controls. In addition, certain FcgammaRIIIa and FcgammaRIIIb gene polymorphisms appear to be associated with an early disease onset, disease severity, the presence of arthritis, and vascular involvement in BD.