Radiosensitivity in a newborn with microcephalia: A case report of Nijmegen breakage syndrome.

AIM: Nijmegen breakage syndrome (NBS) is an autosomal recessive DNA repair disorder which is characterized by immunodeficiency and increased risk of lymphoproliferative malignancy. CASE: We observed an increase in the rate of chromosomal rearrangements in the cultured cells following an incidental radiograph for craniosynostosis in a newborn who was followed up due to microcephaly. We identified a homozygous deletion of c.657_661delACAAA/p.Lys219fs (rs587776650) in the NBN gene through whole exome sequencing. CONCLUSION: It is crucial to thoroughly examine the clinical features of newborns with microcephaly and consider chromosomal instability syndromes just like Nijmegen breakage syndrome. Not overlooking radiosensitivity, which is a characteristic feature of this syndrome, is a vital condition to the patient's survival time.

Investigation of the relationship between IL17A, IL17F and ILR1N polymorphisms and COVID-19 severity: The predictive role of IL17A rs2275913 polymorphism in the clinical course of COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the mortality rate of the disease has been relatively under control as of 2022, more than 15 million confirmed COVID-19 cases have been detected in Turkey to date, causing more than 100,000 deaths. The clinical manifestation of the disease varies widely, ranging from asymptomatic to acute respiratory distress syndrome causing death. The immune response mechanisms have an important impact on the fine adjustment between healing and enhanced tissue damage. This study aims to investigate the relationship between the variants of the interleukin 1 receptor antagonist (IL1RN), interleukin 17A (IL17A), and interleukin 17F (IL17F) genes and COVID-19 severity. The study population comprised 202 confirmed COVID-19 cases divided into three groups according to severity. The IL1RN variable number of a tandem repeat (VNTR) polymorphism was genotyped by polymerase chain reaction (PCR), and IL17A rs2275913, IL17F rs763780 and rs2397084 polymorphisms were genotyped by the PCR-based restriction fragment length polymorphism method. Statistical analysis revealed a significant association between IL17A rs2275913 variant and COVID-19 severity. The AA genotype and the A allele of IL17A rs2275913 were found significant in the severe group. Additionally, we found a significant relationship between haplotype frequency distributions and severity of COVID-19 for the IL17F rs763780/rs2397084 (p = 0.044) and a combination of IL17F rs763780/rs2397084/ IL17A rs2275913 (p = 0.04). The CG and CGA haplotype frequencies were significantly higher in the severe group. IL17A rs2275913, IL17F rs763780 and rs2397084 variants appear to have important effects on the immune response in COVID-19. In conclusion, variants of IL17A rs2275913, IL17F rs763780 and rs2397084 may be the predictive markers for the clinical course and potential immunomodulatory treatment options in COVID-19, a disease that has placed a significant burden on our country.

The 3'UTR region of the DNA repair gene PARP-1 May increase the severity of COVID-19 by altering the binding of antiviral miRNAs.

COVID-19 may cause the release of systemic inflammatory cytokines resulting in severe inflammation. PARP-1 has been identified as a nuclear enzyme that is activated by DNA strand breaks. It has been suggested that PARP-1 has a role in the cytokine storm shown as a cause of mortality in COVID-19, and its inhibition may adversely affect the replication of SARS -CoV-2. We aimed to investigate the relationship between PARP-1 gene polymorphisms and the clinical severity of COVID-19. rs8679 TT genotype was found to increase with the COVID-19 disease severity. The 3'UTR polymorphism rs8679 may cause PARP-1 activity as a result of viral replication increase by changing the binding site of antiviral or anti-inflammatory miRNAs. PARP-1 may affect the severity of COVID-19 by cytokine release and maybe a possible treatment target.

Association of NOD1 and NOD2 Polymorphisms With Susceptibility to Subacute Sclerosing Panencephalitis.

Background: Subacute sclerosing panencephalitis is a progressive neurodegenerative disease that is a late complication of measles infection. However, to date, the pathogenesis of subacute sclerosing panencephalitis is still not explained; both viral and host factors seem to be associated. The present study aimed to investigate the relationship between NOD1 and NOD2 gene variants and subacute sclerosing panencephalitis. Methods: The gene variants of NOD1 (rs2075820 and rs2075818) and NOD2 (R334Q and R334W) were explored in 64 subacute sclerosing panencephalitis patients and 70 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of the AA genotype and A allele of rs2075820 (NOD1; c.796G>A) polymorphism were lower in patients compared with controls (P = .022 and .014, respectively). The presence of the A allele of rs2075820 may be considered as a protective factor for subacute sclerosing panencephalitis. There was a significant difference between the groups in rs2075818 (NOD1 G/C) polymorphism, and the CC genotype increased the risk of subacute sclerosing panencephalitis by 3.471-fold. The carriers of the C allele of rs2075818 (G/C) had a 1.855-fold susceptibility to subacute sclerosing panencephalitis (P = .018). The GC genotype might be associated with subacute sclerosing panencephalitis susceptibility in the patients compared with patients without having that haplotype (P = .03). Conclusions: Thus, we identified an association between subacute sclerosing panencephalitis and the rs2075820 (NOD1 G/A) and rs2075818 (NOD1 G/C) polymorphisms. These findings implicate a possible effect of this genetic polymorphism in susceptibility to subacute sclerosing panencephalitis, which needs to be confirmed in bigger populations.

Association between Psoriasis Disease and IFN-λ Gene Polymorphisms.

Psoriasis is one of the most common chronic immune-mediated skin diseases, having a strong genetic predisposition. Psoriasis is a T-cell-mediated disease with a mixed Th1/Th17 cytokines environment. IL-23/IL-17 axis hyperactivation is the primary pathogenesis. Psoriasis lesions have been known to exhibit high IFN-λ1 and IFN-stimulated genes (ISGs) expression, which appears to be driven by Th17 cells. However, the role and mechanism of IFN-λs in psoriasis disease remains unknown. The study aimed to investigate the relationship between IL-28B and IL-29 gene polymorphisms with psoriasis disease and clinical severity. We performed single-nucleotide polymorphisms (SNPs) of IL-28B rs12979860 (IL-28 C/T), rs8099917 (IL-28 T/G), and IL-29 rs30461 (IL-29 T/C) in 140 patients with psoriasis disease and 159 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequency distributions of the rs12979860 (IL-28 C/T) and rs30461 (IL-29 T/C) polymorphisms were similar in the patient and control groups and were not statistically significant. The TG genotype of rs8099917 was statistically significantly different in patients from both groups. The TG genotype increased the risk of disease1.9-fold. The G allele may be associated with the pathogenesis of psoriasis.

Association between IL-18 gene polymorphisms and Hashimoto thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT), which is also called lymphocytic thyroiditis, is the most frequent autoimmune thyroid disease (AITD), in which T helper-1 lymphocytes mediate the disease. IL-18 is expressed in thyroid follicular cells (TFCs) during HT. The findings of studies aimed at investigating the relationship between IL-18 and HT are highly contradictory. In this study, we aimed to investigate the association between IL-18 gene polymorphisms and HT. METHODS AND RESULTS: The study included 97 patients diagnosed with HT and 86 volunteers in the healthy control group. The IL18-607C/A (rs1946518) and -137G/C (rs187238) genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. No significant difference in the mean age or sex was observed between the groups (p = 0.763 and p = 0.658, respectively). The -137 IL18 CG genotype was more frequent in HT patients than in controls. In HT patients, the risk of the IL-18 CG genotype was more than 2.237 times higher (OR 2.237%95 Cl 1.195-4.187, p = 0.039) than that of the G/G genotype. Additionally, the -607 AC genotype was more frequent in the control group than in the HT group (in individuals with the IL18 CG genotype). CONCLUSIONS: According to our results, the CG genotype might be a risk factor for HT. Conversely, there is a possibility that the AC genotype plays a protective role against the condition. However, further studies will contribute to new solutions by revealing the molecular and cellular mechanisms of HT.

Association of NOD1, NOD2, PYDC1 and PYDC2 genes with Behcet's disease susceptibility and clinical manifestations.

Purpose: Behçet's disease (BD) is an autoinflammatory disease with clinical manifestations such as mucocutaneous, ocular, vascular, gastrointestinal, musculoskeletal and central nervous system involvement. Features of innate and adaptive immunity and inflammasome pathways have been claimed in the pathogenesis of BD. We aimed to investigate the roles of NOD1, NOD2, PYDC1 and PYDC2 genes in the genetic predisposition of BD.Materials and Methods: Genetic variations of NOD1 (rs2075820 and rs2075818) and NOD2 (R334Q and R334W) genes were explored in 68 BD patients and 70 controls with PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) approach. PYDC1 and PYDC2 gene variants were investigated by Sanger sequencing.Results: The polymorphism of rs2075820 (NOD1 G/A) had a statistically significant difference between the BD and controls, AA genotype was 2.460-fold protective. When compared in terms of cardiovascular involvement in BD patients, AA genotype was increased the risk of cardiovascular involvement 4.286-fold. There was a significant difference between BD and controls in rs2075818 (NOD1 G/C) polymorphism and CC genotype increased the risk of BD by 3.780-fold. In terms of rs2075818 variants, there was a statistically significant difference between BD patients with ocular lesions, joints, cardiovascular and gastrointestinal involvement and controls. There was a significant difference between the patients with joint involvement and controls and the risk increased of 3.310-fold.Conclusion: The data shed new light on the association between polymorphisms of NOD1 gene and BD and clinicial manifestations. However, NOD2, PYDC1 and PYDC2 genes were not associated with BD in the Turkish population.

Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19: A case study.

Coronavirus disease 2019 (COVID-19) is an infectious disease, and the reason behind the currently ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme (ACE2) has been recognized as the specific receptor of the SARS-CoV-2 virus. Although the possible effect of ACE2 gene polymorphism remains unknown, human ACE2 receptor expression influences SARS-CoV-2 susceptibility and COVID-19 disease outcome. In this study, we aimed to investigate the relationship between ACE gene I/D polymorphism, ACE2 receptor gene polymorphism, and COVID-19 severity. ACE gene insertion/deletion (I/D) polymorphism and ACE2 receptor gene rs2106809 and rs2285666 polymorphisms were determined using polymerase chain reaction (PCR) and PCR-based restriction fragment length polymorphism methods, respectively, in 155 COVID-19 patients who were divided into three groups (mild, moderate, and severe) according to clinical symptoms. However, the distribution of genotype and allele frequencies of ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not statistically significant in all groups. In conclusion, in the study population, ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not associated with the severity of COVID-19 infection. Although ACE2 receptor gene expression may affect the susceptibility to COVID-19, there is no existing evidence that the ACE or ACE2 gene polymorphisms are directly associated with COVID-19 severity. Interindividual differences in COVID-19 severity might be related to epigenetic mechanisms of ACE2 receptor gene expression or variations in other genes suggested to play a critical role in COVID-19 pathogenesis such as pro-inflammatory cytokines and coagulation indicators.

A bioinformatic approach to investigating cytokine genes and their receptor variants in relation to COVID-19 progression.

Severe acute respiratory syndrome coronavirus 2 infection produces a wide spectrum of manifestations, ranging from no symptom to viral pneumonia. This study aimed to determine the genetic variations in cytokines and their receptors in relation to COVID-19 pathogenesis using bioinformatic tools. Single nucleotide polymorphisms (SNPs) of genes encoding the cytokines and cytokine receptors elevated in patients with COVID-19 were determined from the National Biotechnology Information Center website (using the dbSNP database). Missense variants were found in 3 cytokine genes and 10 cytokine receptor genes. Computational analyses were conducted to detect the effects of these missense SNPs via cloud-based software tools. Also, the miRSNP database was used to explore whether SNPs in the 3'-UTR altered the miRNA binding efficiency for genes of cytokines and their receptors. Our in silico studies revealed that one SNP in the vascular endothelial growth factor receptor 2 (VEGFR2) gene was predicted as deleterious using sorting intolerant from tolerant. Also, the stability of VEGFR2 decreased in the I-Mutant2.0 (biotool for predicting stability changes upon mutation from the protein sequence or structure) prediction. It was suggested that the decrease in VEGFR2 function (due to the rs1870377 polymorphism) may be correlated with the progression of COVID-19 or contribute to the pathogenesis. Moreover, 27 SNPs were determined to affect miRNA binding for the genes of cytokine receptors. CXCR2 rs1126579, TNFRSF1B rs1061624 and IL10RB rs8178562 SNPs were predicted to break the miRNA-mRNA binding sites for miR-516a-3, miR-720 and miR-328, respectively. These miRNAs play an important role in immune regulation and lung damage repair. Further studies are needed to evaluate the importance of these miRNAs and the SNPs.

The relationship among androgens, insulin resistance and ghrelin polymorphisms in post-adolescent male patients with severe acne vulgaris.

INTRODUCTION: Ghrelin has anti-inflammatory and immunomodulatory activities. Data about the role of ghrelin and ghrelin polymorphisms in the development of acne vulgaris in post-adolescent male patients are limited. AIM: To evaluate the role of serum androgens, insulin resistance, ghrelin and ghrelin polymorphisms in severe acne vulgaris. MATERIAL AND METHODS: Thirty-five post-adolescent male patients with a mean age of 28.0 ±5.4 years and 33 age-and BMI-matched controls were enrolled. Serum androgens, lipids, insulin sensitivity parameters and ghrelin levels were determined. The PCR method was used for GHRL polymorphisms (rs27647, rs696217 and rs34911341 genotypes). RESULTS: Patients had similar anthropometric measures to controls, except a significantly higher WHR in patients (0.92 ±0.06 vs. 0.86 ±0.08, p < 0.05). Also, FPG, HOMA-IR values, lipid profile and serum androgen levels were similar. Interestingly, patients had significantly lower ghrelin levels than controls (4.5 ±5.8 vs. 101.2 ±86.5 pg/ml, p < 0.001). The frequencies of rs696217 and rs34911341 genotypes were similar whereas the distribution of rs27647 alleles was significantly different between the groups (p < 0.05). GA and GG genotypes of GHRL rs27647 polymorphism indicated an increased risk of developing acne vulgaris (OR = 11.156, 95% CI: 2.864-43.464, OR = 5.312, 95% CI: 1.269-22.244, respectively; p < 0.05). Patients with rs27647-AA polymorphism had significantly lower GAGS scores than other groups (AA genotype 6.7 ±14.1 vs. GA genotype 24.6 ±15.7 and GG genotype 19.4 ±17.9, p < 0.001). None of the polymorphisms had a significant effect on metabolic parameters, insulin sensitivity and serum ghrelin levels. CONCLUSIONS: Decreased ghrelin levels and GA and GG genotypes of GHRL gene rs27647 polymorphism may have a role in the pathogenesis of acne vulgaris.

The effect of FOXO gene family variants and global DNA metylation on RRMS disease.

Multiple sclerosis is a chronic disease that usually occurs with exacerbations and remissions in young adults, affects the central nervous system white matter in multiple localization, and is thought to be the result of complex interactions of genetic and environmental factors, the most common form is relapsing-remitting MS. Forkhead transcription factors O class (FOXO) are responsible for the regulation of various cellular processes including cell cycle, apoptosis, DNA repair, cellular resistance and metabolism. DNA methylation is such an epigenetic change and has been shown to be associated with almost any biological process. The aim of our study to show the relation between the genetic variants of FOXO3a (rs2253310 rs4966936) and FOXO1 (rs3900833, rs4581585) and global DNA methylation in RRMS. We analyzed DNA obtained from 79 RRMS patients and 104 healthy individuals by PCR-RFLP method for the detection of genetic variants. For the determination of global DNA methylation, results were obtained using ELISA method. The data were evaluated statistically. As a result of our analysis; global DNA methylation is higher in RRMS patients compared to control individuals and it can be effective on the disease. In addition, it has been determined that variants of FOXO3a (rs2253310, rs4966936) and FOXO1 (rs3900833), which have been genotyped, may be effective in disease pathogenesis. These results suggest that DNAmethylation and FOXO gene variants may be effective in neuronal loss in RRMS.

Novel SNARE Complex Polymorphisms Associated with Multiple Sclerosis: Signs of Synaptopathy in Multiple Sclerosis

Background: It is well known that axonal degeneration plays a role in disability in patients with multiple sclerosis, and synaptopathy has recently become an important issue. Aims: To investigate the possible roles of selected synaptic and presynaptic membrane protein genetic polymorphisms (VAMP2, SNAP-25, synaptotagmin, and syntaxin 1A) in patients with multiple sclerosis. Study Design: Case-control study. Methods: A total of 123 patients with multiple sclerosis and 192 healthy controls were included. The functional polymorphisms of specific SNARE complex proteins (VAMP2, synaptotagmin XI, syntaxin 1A, and SNAP-25) were analyzed by polymerase chain reaction. Results: Significant differences were detected in the genotype and allele distribution of 26-bp Ins/Del polymorphisms of VAMP2 between patients with multiple sclerosis and control subjects; Del/Del genotype and Del allele of VAMP2 were more frequent in patients with multiple sclerosis (p=0.011 and p=0.004, respectively). Similarly, Ddel polymorphism of SNAP-25 gene C/C genotype (p=0.059), syntaxin 1A T/C and C/C genotypes (p=0.005), and synaptotagmin XI gene C allele (p=0.001) were observed more frequently in patients with multiple sclerosis. CC, syntaxin rs1569061 1A gene for 33-bp promoter region TC haplotypes, and synaptotagmin XI gene were found to be associated with an increased risk for multiple sclerosis (p=0.012). Similarly, GC haplotype for rs3746544 of SNAP-25 gene and rs1051312 of SNAP-25 gene were associated with an increased risk for multiple sclerosis (p=0.022). Conclusion: Genetic polymorphisms of SNARE complex proteins, which have critical roles in synaptic structure and communication, may play a role in the development of multiple sclerosis.

IL28B, IL29 and micro-RNA 548 in subacute sclerosing panencephalitis as a rare disease.

Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease which affects children and young adults, caused by a persistent infection of defective measles virus. IFN-λs (IL-28A, IL-28B and IL-29) are a group of cytokines mediating antiviral responses. It has been shown that IL-29 levels are significantly higher in infected cells with defective measles virus. IL-29 expression is thought to be regulated at post-transcriptional level and miRNA-548 family targets the 3'UTR of the IFNL1 gene. Impaired immune system has an important role as well as viral factors in SSPE. The aim of our study investigates whether IL-28B, IL-29 levels and gene polymorphisms contribute to the damaged immune response leading to the development of SSPE. Also possible association of miR-548 family with IL-29 and SSPE is explored. Frequencies of rs12979860, rs8099917, rs30461, serum levels of IL-28B, IL-29 and expression levels of miR-548b, miR-548c, miR-548i are determined at 64 SSPE patients and 68 healthy controls. Serum IL-29 levels are statistically significant higher in SSPE patients. Allele frequencies of rs8099917 are statistically significant higher in SSPE patients and resulted G allele is found to increase 2.183-fold risk of SSPE. The expression levels of miR-548b-5p, miR-548c-5p and miR-548i are found to be statistically significant higher in SSPE patients. Dramatically increased level of IL-29 seen in patient group indicates that the elevated miR-548 expression is compensatory result of the over-activated immune system response. Further studies referred to IL28, IL29 and related miRNA's will be enlightened the pathogenesis of SSPE.

The Role of Forkhead Box Class O3A and SIRT1 Gene Variants in Early-Onset Psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder, which is characterized by a heightened immunological response. Although the immunogenetics of this chronic inflammatory disorder is poorly understood, its expression is known to be dependent on proinflammatory cytokines. It is known that two distinct subtypes of chronic plaque psoriasis: Early-onset psoriasis (EOP) before the age of 40 years and late-onset psoriasis after the age of 40 years. Forkhead box class O3A (FOXO3A) is a transcription factor, which plays an important role in cell-cycle regulation, apoptosis, oxidative stress, and DNA repair. The silent information regulator (SIRT) is thought to have a role in skin disorders, including psoriasis, that are characterized by hyperproliferation and inflammation. AIM: The aim of this study was to investigate FOXO3A and SIRT1 gene polymorphisms in EOP. METHODS: The study group consisted of 142 EOP patients and 123 unrelated healthy controls. FOXO3A polymorphisms were determined using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. SIRT1 gene polymorphisms were determined by PCR-confronting two-pair primers methods. RESULTS: The FOXO3A rs4946936 and SIRT1 rs7069102 gene polymorphisms were positively correlated with EOP and disease severity. The GG genotype frequency of SIRT1 rs7069102 gene polymorphisms was increased in severe EOP. The CC frequency of FOXO3A rs4946936 was increased in EOP with nail disorders. CONCLUSION: The rs7069102 gene polymorphism of SIRT1 and rs4946936 polymorphism of FOXO3A are associated with early onset psoriasis; this may be responsible for increased keratinocyte proliferation in the pathogenesis of psoriasis and disease severity.

Increased Serum Levels of IL-28 and IL-29 and the Protective Effect of IL28B rs8099917 Polymorphism in Patients with Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is thought to result from decreased T helper type 2 (Th2) responses, leading to the progressive destruction of thyrocytes. IFN-λ1, -λ2, and -λ3 (also known as IL-29, IL-28A, and IL-28B, respectively) are recently described members of the IFN-λ family and have been shown to decrease the production of Th2 cytokines in vitro. However, the role and mechanism of IFN-λ1 in HT remain unknown. The purpose of this study was to examine whether IL29 and IL28B gene polymorphisms are susceptibility genes for the development of HT. Also, we investigated the effects of IL-29 and IL-28 serum levels in the pathogenesis of HT. Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, single-nucleotide polymorphisms (SNPs) of IL28B rs8099917 (IL28 G/T) and IL29 rs30461 (IL29 T/C) were studied in 99 patients with HT and 100 healthy controls. Considering the allelic distribution of the IL28 G/T polymorphism, a higher frequency of the G allele was observed in the control group versus the HT group. Thus, it was suggested that the G allele may be protective against HT pathogenesis (OR = 0.388, 95% CI = 0.217-0.693; p = 0.001). Our findings also demonstrated that there was a statistically significant difference in serum IL-28 and IL-29 levels between case and control groups (p < 0.001). Increased serum levels of IL-28 and IL-29 were found in patients with HT. However, we did not find a relationship between the IL29 gene polymorphism and HT. In conclusion, the IL28B gene polymorphism and serum IL-28 and IL-29 levels seem to play a role in the pathogenesis of HT.

[Investigation of the association between chronic hepatitis B and C infections and TNF-α (-308) gene polymorphism]. / Kronik hepatit B ve C enfeksiyonlari ile TNF-α (-308) gen polimorfi zmi arasindaki iliskinin arastirilmasi.

Cytokines and genetic factors play important roles in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) infections. Variations in cytokine genes may effect the gene expression and may lead to changes in the clinical manifestations of diseases. One of the single nucleotide polymorphisms in the promoter region of tumor necrosis factor-alpha (TNF-α) gene is the polymorphism at -308. position which was investigated in many studies by means of its relationship between CHB and CHC infections, however their results are incompatible. Furthermore, there is no sufficient data on this subject in our country. This study was aimed to determine the relationship between TNF-α(-308) gene polymorphism with CHB and CHC infections. A total of 271 patients with chronic hepatitis and 181 healthy subjects were included in the study. Of them 167 were CHB cases (67 female, 100 male; age range 18-74 years, mean age: 40.23 ± 13.09) and 95 controls for CHB group (46 female, 49 male; mean age: 36.41 ± 15.0 years), while 104 were CHC cases (63 female, 41 male; age range: 25-79 years, mean age: 52.8 ± 12.6) and 86 controls for CHC group (41 female, 45 male; mean age: 36.4 ± 14.9 years). After the isolation of genomic DNA from blood samples of the patient and control groups, TNF-α(-308)G/A (rs 1800629) polymorphism was investigated by using the real-time polymerase chain reaction from the obtained DNAs. Among CHB group, TNF-α(-308) GG, GA, AA genotypes were detected in 126 (75.4%), 38 (22.8%) and 3 (1.8%) of the patients, respectively, while these numbers were 84 (88.4%), 11 (11.6%) and 0 (0%) in control group, respectively. Among CHC group, TNF-α(-308) GG, GA, AA genotypes were detected in 37 (35.6%), 28 (26.9%) and 39 (37.5%) of the patients, respectively, while these numbers were 38 (44.2%), 8 (9.3%) and 40 (46.5%) in control group, respectively. The frequency of GA genotype was significantly higher in both patient groups compared to the control groups (p=0.024 for CHB and p= 0.006 for CHC). When the distribution of allele frequencies of TNF-α(-308)G/A polymorphism was evaluated in the patients and control groups, it was noted that G allele was found to be high in CHB patients comparing with controls (94.2% vs 86.8%), however A allele was identified to be lower than controls (5.8% vs 13.2%) (p= 0.008). In contrast, there was no significant difference in terms of allele frequency compared with CHC patients and the control group (p= 0.969). In conclusion, our data in accordance with the results of many studies in literature, determined that TNF-α(-308) polymorphisms can influence the chronicity of hepatitis B and C infections. Further studies on this subject would contribute to the elucidation of the molecular mechanisms of chronic hepatitis B and C diseases.

Serum paraoxonase level and paraoxonase polymorphism in patients with acromegaly.

BACKGROUND: Acromegalic patients have increased cardiometabolic risk factors due to an elevation of growth hormone (GH) levels. Human serum paraoxonase (PON), a high-density lipoprotein (HDL)-related enzyme, is one of the major bioscavengers and decreases the oxidation of low-density lipoprotein (LDL), a key regulator in the pathogenesis of atherosclerosis. In this study, we investigated a potential relationship between serum PON levels or PON polymorphisms and acromegaly. METHODS: A total of 48 acromegalic patients and 44 healthy controls were included in this study. Serum GH levels, insulin-like growth factor-1 levels and lipid profiles were measured. Serum PON levels, as well as PON 1 L55M and Q192R gene polymorphisms, were examined. RESULTS: No significant differences were found in terms of age, gender, presence of diabetes, serum LDL cholesterol (LDL-C), HDL-C, or triglyceride levels between the case and control groups (P > 0.05). A statistically significant difference was found in serum PON levels between the cases and controls (P = 0.007). The median serum PON level was 101 ± 63.36 U/l in the case group and 63 ± 60.50 U/l in the control group. There was a significant correlation between serum PON levels and IGF-1 levels (P = 0.004, r = 0.319); however, no significant differences were found in PON1 L55M and PON Q192R polymorphisms between the patients and controls (P = 0.607 and P = 0.308, respectively). In addition, no significant differences were found in serum PON levels in acromegalic patients who were and were not in remission (P = 0.385), nor between those with PON1 L55M and Q192R polymorphisms (P = 0.161 and P = 0.336, respectively). CONCLUSIONS: Elevated serum PON levels were detected in acromegalic patients, independently of their remission status. This suggests protective effects for cardiometabolic risk parameters.

Homozygous Ala65Pro Mutation with V89L Polymorphism in SRD5A2 Deficiency.

OBJECTIVE: Deficiency of steroid 5-alpha reductase type 2 (5αRD2) is a rare autosomal recessive disorder caused by mutations in the SRD5A2 gene. A defect in the 5-alpha reductase enzyme, which ensures conversion of testosterone into dihydrotestosterone, leads to disorders of sex development. This study presents the clinical and genetic results of patients with 5αRD2 deficiency. METHODS: 5αRD2 deficiency was detected in 6 different patients from 3 unrelated families. All patients were reared as girls. Two of the patients presented with primary amenorrhea, one with primary amenorrhea and rejection of female gender, and the others with masses in their inguinal canals. Chromosome and sex-determining region Y (SRY) gene analyses were performed in all patients. Additionally, five exons of the SRD5A2 gene were amplified with polymerase chain reaction in the obtained DNA samples and evaluated. RESULTS: While 46,XY was identified in 5 patients, 47,XXY was detected in one patient. The SRY gene was positive in all patients. The p.Ala65Pro (c193G>C) mutation and V89L polymorphism were observed in exon 1 of the SRD5A2 gene in all patients. CONCLUSION: Identification of this mutation and polymorphism is a significant indicator of presence of 5αRD2 deficiency in Southeastern Turkey, a geographical region where consanguineous marriages are also highly common.

Partial trisomy 4q and partial monosomy 9p in a girl with choanal atresia and various dysmorphic findings.

We report a new-born girl with partial trisomy of 4q28-qter and partial monosomy of 9p24-9ter. Our patient has choanal atresia, hypertelorism, wide nasal bridge, high arched palate, discrete nipples, heart defects, myoclonic seizures and various dysmorphic findings. Standard chromosomal analysis with G-banding with Trypsin-Giemsa revealed 46,XX,der(9)t(4;9)(q28;p24) resulting from the mother's t(4,9) (q28;p24) karyotype. Deletions of the terminal part of 9p and partial trisomy of chromosome 4q are rare chromosomal alterations. To our knowledge, this is the first report of choanal atresia in a patient with a partial trisomy of 4q28-qter and partial monosomy 9p24-9ter combination, which were detected by integrated cytogenetic and genomic analysis.

The relation of PON1-L55M gene polymorphism and clinical manifestation of Behcet's disease.

PURPOSE: Behçet's disease is a multisystem disease characterized by recurrent oral and genital ulcers, relapsing uveitis, mucocutaneous, articular, gastrointestinal, neurologic, and vascular manifestations. Paraoxonase is believed to play an important role in protection of LDL and HDL particles from oxidation, in antioxidant effect against lipid peroxidation on cellular membranes, and in anti-inflammatory process. Lipid peroxidation and free oxygen radicals have been thought to play a role in pathogenesis of BD. The association of paraoxonase gene polymorphisms with Behçet's Disease in a group of Turkish patients with clinical manifestations and healthy controls has been investigated. PATIENTS AND METHODS: Paraoxonase (PON-1-L55M) gene polymorphism was investigated in 50 Behcet patients and 50 healthy individuals with a PCR/RFLP method. RESULTS: There were significant differences between patients and the control group in allele frequencies of the PON1 L55M polymorphism (p=0.04). Also, when patients were compared with the control group according to clinical manifestations, this statistical significance was getting sharper. Compared with the PON55 L allele, the M allele was associated with greater than 3.5 fold (OR 3.5, 95% CI 1.3-8.9) increased risk of ocular (OR 2.4, 95% CI 1.1-5.3), 2.4 fold joint and 3.1 fold (OR 3.1, 95% CI 1.1-8.4) central nervous system manifestations of BD. CONCLUSION: The PON L55M gene polymorphism seemed to play a role in the pathogenesis of BD.