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Author(s): Mustafa Koyun [sup.1] , Muhammet Sancaktar [sup.1] , Gülsah Kaya Aksoy [sup.1] , Elif Çomak [sup.1] , Ayla Kaçar [sup.1] , Mehtap Adar [sup.1] , Afig Berdeli [sup.2] , [...]

Author(s): Mustafa Koyun [sup.1] , Muhammet Sancaktar [sup.1] , Gülsah Kaya Aksoy [sup.1] , Elif Çomak [sup.1] , Ayla Kaçar [sup.1] , Mehtap Adar [sup.1] , Afig Berdeli [sup.2] , [...]

Abstract The aim of this study was to assess the association between metabolic control, microalbuminuria, and diabetic nephropathy with ambulatory blood pressure monitoring (ABPM) in normotensive individuals with type 1 [...]

Abstract The aim of this study was to determine the distribution of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, and its effects on clinical, laboratory, histological findings, treatment responses [...]

Abstract 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 [...]

Byline: Hakan Erdogan (1), Sevgi Mir (1), Erkin Serdaroglu (1), Afig Berdeli (2), Nejat Aksu (3) Keywords: ACE gene polymorphism; Vesicoureteric reflux; Renal scarring Abstract: The possible relationship between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and renal scarring secondary to vesicoureteral reflux (VUR) has recently attracted attention and the DD genotype was postulated to be a risk factor for renal scarring. However, available data represent conflicting results. The aim of this study was to investigate the ACE gene I/D polymorphism and the other known risk factors for renal scarring in children with low- and high-grade VUR. The study included 96 (67 females, 29 males) patients (mean age at diagnosis 3.7+-3.3 years) with VUR that were assessed for ACE I/D gene polymorphism. ACE genotypes were determined as II, ID, and DD using the polymerase chain reaction. The control group consisted of 103 healthy children with the same ethnicity to find the distribution of ACE gene I/D polymorphism in the population. The frequency of renal scarring was 80.8% in the high-grade reflux group and 34.3% in the low-grade reflux group. There was no difference between groups with renal scarring and without scarring with respect to gender, family history of VUR, age at diagnosis of VUR, associated urological abnormalities, frequency of urinary tract infection episodes, and the occurrence of bilateral or unilateral VUR. Genotype DD was found to be a significant risk factor for renal scarring in the study group by multivariate regression analysis (odds ratio 3.79, P=0.011). It was not a risk factor in high-grade reflux patients (odds ratio 0.60, P=0.62). However, it was a risk factor in low-grade patients with respect to renal scarring (odds ratio 4.0, P=0.024). Although renal scarring is not common in low-grade reflux patients, there may be scarring in some patients. DD polymorphism of the ACE gene is a significant risk factor in low-grade reflux patients with renal scarring. Author Affiliation: (1) Department of Pediatric Nephrology, Ege University Medical School, 35100 Izmir, Turkey (2) Department of Pediatrics, Laboratory of Molecular Medicine, Ege University Medical School, Izmir, Turkey (3) Department of Pediatric Nephrology, SSK Tepecik Teaching Hospital, Izmir, Turkey Article History: Registration Date: 26/03/2004 Received Date: 20/10/2003 Accepted Date: 12/03/2004 Online Date: 12/05/2004

Commentary The diagnosis of UMOD storage disease should be suspected based on clinical features and confirmed by genetic testing without the need for renal biopsy. In patients with asymptomatic renal [...]

Case summary This 15-year-old girl was the only child born to nonconsanguineous parents of Turkish background. She showed normal development and had an unremarkable history. She was admitted with right [...]

Uveitis is a chronic inflammatory disease. Chronic inflammation has been shown to have a role in pathogenesis of atherosclerosis. Atherosclerosis is the most important risk factor of cardiovascular diseases and is shown to start as early as childhood. In this study, we investigated the presence of subclinical atherosclerosis in children with uveitis. Seventy five patients who were diagnosed as having uveitis in ophthalmology and pediatric rheumatology clinics were included in the study. Patients with hypertension, obesity, dyslipidemia, diabetes, and with history of early cardiovascular disease were excluded. Arterial stiffness, carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), and carotid artery intima-media thickness (cIMT) were measured for each patient. These measurements were compared with 50 healthy children with similar age and sex as controls. The mean age of patients in this study was 12.24 ± 2.69 years, and the mean age of controls was 11.32 ± 4.52 years. PWV and AIx values were higher in the patient group (p = 0.04, p = 0.03). cIMT levels were not different in patient and control groups. When patients were grouped as having uveitis for more than 5 years or not, patients with longer duration of uveitis had higher PWV, AIx, and cIMT levels (p values were 0.01, 0.02, and 0.04 respectively). Vascular functions deteriorate first with endothelial damage in children with uveitis and as disease continues, increase in cIMT is added. We think that for follow-up of the disease and evaluation of the treatment, non-invasive subclinical atherosclerosis markers should be used along with activation criteria of primary diseases.

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.

B lymphocyte subpopulations, previously defined classification schemes (Freiburg, Paris, EuroClass), TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF13 (APRIL) gene mutations, CTLA-4 and ICOS gene polymorphisms were analyzed in 25 common variable immunodeficiency (CVID) patients and 25 healthy controls. Patients were also divided into two subgroups due to some disease severity criteria. SG (severe disease group) (n:11) included patients who have splenomegaly and/or granulomatous diseases and/or bronchiectasis and/or lower baseline IgG values (<270 mg/dl). MG (moderate disease group) (n:14) patients diagnosed as having ESID/PAGID criteria but does not fulfill SG inclusion criteria. The onset of infectious symptoms and age at diagnosis were 50.0 ± 45.7 and 78.5 ± 54.5 months, respectively. Parental consanguinity rate was 54.5% in SG and 7.1% in MG. Switched-memory B cells (CD19 + 27 + IgD-IgM-) showed significant decrease in CVID patients and these cells were also significantly lower in SG compared to MG. CVID patients had significantly higher percentages of CD19 + κ + B cells and CD19 + λ + B cells than healthy controls. Freiburg classification: 87.5% of patients (n:21) were in group I and 12.5% were in Group II. Eighteen (75%) CVID patients with a low percentage of CD21(low) B cells were in Group Ib while three patients classified as Group Ia. The significantly lower levels of IgG and IgA in Group Ia is a novel finding. The percentages of patients for Paris Classification groups MB0, MB1, MB2 were 88%, 4% and 8%, respectively. There was a significant increase of splenomegaly, lymphadenopathy and autoimmune cytopenia in Group MB0. EuroClass: 45.8% of patients were smB+ and 54.2% were smB-. Splenomegaly and lymphadenopathy were significantly higher in smB- group. TACI: One patient carried heterozygous C104R mutation which was known as disease causing. APRIL: G67R and N96S SNPs were detected in most of the patients and healthy controls. BAFF-R: P21R/H159Y compound heterozygous mutation (n:1) and P21R heterozygous mutations (n:3) were detected. +49 A > G changes in exon 1 of CTLA-4 gene: GG and AG genotypes increase the risk of CVID development 1.32 and 2.18 fold, respectively. 1564 T > C polymorphisms on 3'UTR region in exon 2 of ICOS gene was not found to be significantly different in CVID patients. CVID classifications were not helpful in determining the genetic etiology of CVID.

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).

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.

Objective: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. Chronic inflammation has been reported to be a risk factor for thyroid neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with thyroid cancer. We aimed to evaluate the relation between the genotypic and allelic frequencies of the IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) polymorphisms, and their association with the risk of developing papillary thyroid cancer (PTC) in the Turkish population., Research Design and Methods: Forty-two patients with PTC and 113 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for IL-10 gene polymorphism was performed using PCR-restriction fragment length polymorphism method., Results: Statistically significant difference IL-10(-1082 G/A) gene polymorphism was determined between 2 (PTC and control) groups. No difference was determined with respect to IL-10(-592 A/C) and IL-10(-819 C/T) gene polymorphisms, and IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) allele frequencies of participating between the control group and the patients with PTC (p>0.05)., Conclusions: The polymorphism of IL-10(-1082 G/A) gene was significantly associated with the occurrence of PTC. Such studies will contribute significantly to our understanding of the biological role of IL-10(-1082 G/A) gene polymorphism in PTC development. In conclusion, IL-10(-1082 G/A) gene polymorphism may affect the survival of papillary thyroid carcinoma.

Objective: Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular (CD) diseases. Cardiovascular risk factors that have been reported include oxidative stress markers [nitric oxide (NO), malondialdehyde (MDA), disulphite (SH)]. We aimed to evaluate the relation between the IL-6 G/C gene polymorphism and oxidative stress markers in polycystic ovary syndrome (PCOS) patients., Design and Patients: We studied 85 PCOS patients and 115 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria., Results: The genotype IL-6 distribution did differ between the control group (CC 9.6%, GC 63.4%, GG 27.0%) and the PCOS patients (CC 4.7%, GC 29.4%, GG 65.9%) (p<0.001). The frequency of the polymorphic G allele was also not similar for the group with PCOS as for the control group with 80.6% and 58.7%, respectively (p<0.001). No statistically significant difference was determined for MDA and NO levels in PCOS patients and control group (p>0.05). Only SH levels were found to be high in favor of patient group (p<0.05). No statistically significant difference was determined between IL-6 G/C gene polymorphism and oxidative stress markers in PCOS patients and in the control group., Conclusion: Gene polymorphism of IL-6 -174 G>C is a risk factor for PCOS in Turkish patients. IL-6 gene polymorphisms are not related to NO, MDA, and SH levels in PCOS. Our negative results in risks factors of CV disorders can probably be explained by the fact that metabolic parameters and endothelial systems of patients may not yet be affected in this short period of time.

Purpose: Polycystic ovary syndrome (PCOS) is one of the most encountered endocrine malfunctions. PCOS patients have enhanced activation of the blood coagulation system., Methods: Eighty-six young women with PCOS and 70 healthy control women were included in our study. PCOS patients and controls were matched for age, body mass index, and allele frequency. Genetic analysis of TPAI and PAI-1 were performed in all subjects., Results and Conclusions: No statistically significant differences have been detected about the ratios of genotypes resulting from PAI-1 promotor 4G/5G gene polymorphism. PAI-1 765 4G/5G gene polymorphism and TPA gene's Alu-repeat insertion/deletion (I/D) polymorphism ratios were not different from the controls. In this study it is shown by the analysis of TPA gene's Alu-repeat insertion/deletion (I/D) polymorphism the PCOS patients with genotype II had lowers total cholesterol and LDL-cholesterol levels.

Objective: Fas ligand (FasL) is an apoptotic agent and a member of tumor necrosis factor (TNF) family. FasL exists in cytotoxic T lymphocyte (CTL) and natural killer (NK) cells, and it is increased in tumor cell membrane. On the contrary, CTL and NK are bound to Fas on the surfaces of cell membrane; this triggers apoptosis in cytotoxic cells and leads to their death. This system plays an important role in eliminating viral infections and cancer cells. Malfunction of this system results in the development and spread of the malignancy. This study aims at evaluating the influence of Fas and FasL gene polymorphism in papillary thyroid cancer (PTC) in the Turkish population., Research Design and Methods: Forty-five patients with PTC and 100 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for Fas 670 A/G and FasL 843 C/T gene polymorphism was performed using the PCR-restriction fragment length polymorphism (RFLP) method., Results: The evaluation of Fas/FasL genotype and gene allele frequency did not show statistically significant differences between the patient and control group (p>0.05). In addition, the univariate analysis did not reveal a statistically significant relationship between the size of the nodule and the Fas/FasL gene polymorphism in patients with PTC., Conclusions: As in other types of malignancy, genetic factors in the pathogenesis of PTC may also show changes in different populations. Fas/FasL gene polymorphysms are possible that different mechanisms function in apoptosis balance in PTC development.

Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene -2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the -2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the -2518 (G/A) MCP-1 gene polymorphism (p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA (p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the -2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis (p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference.