Identification of novel variants in ten patients with Hermansky-Pudlak syndrome by high-throughput sequencing.

Background: Hermansky-Pudlak syndrome (HPS) is a rare inherited platelet disorder characterized by bleeding diathesis, oculocutaneous albinism (OCA) and a myriad of often-serious clinical complications. Methods: We established the clinical and laboratory phenotype and genotype of six unrelated pedigrees comprising ten patients with clinical suspicion of HPS; including platelet aggregation, flow cytometry, platelet dense granule content, electron microscopy and high-throughput sequencing (HTS). Results: The clinical presentation showed significant heterogeneity and no clear phenotype-genotype correlations. HTS revealed two known and three novel disease-causing variants. The Spanish patients carried a homozygous p.Pro685Leufs17* deletion (n = 2) in HPS4, or the novel p.Arg822* homozygous variant (n = 1) in HPS3. In the case of two Turkish sisters, a novel missense homozygous HPS4 variant (p.Leu91Pro) was found. In two Portuguese families, genetic studies confirmed a previously reported nonsense variant (p.Gln103*) in DTNBP1 in three patients and a novel duplication (p.Leu22Argfs*33) in HPS6 in two unrelated patients. Conclusions: Our findings expand the mutational spectrum of HPS, which may help in investigating phenotype-genotype relationships and assist genetic counselling for affected individuals. This approach is a proof of principle that HTS can be considered and used in the first-line diagnosis of patients with biological and clinical manifestations suggestive of HPS. Key messages We established the relationships between the clinical and laboratory phenotype and genotype of six unrelated pedigrees comprising ten patients with clinical suspicion of HPS. Molecular analysis is useful in confirming the diagnosis and may offer some prognostic information that will aid in optimizing monitoring and surveillance for early detection of end-organ damage. This approach is a proof of principle that HTS can be considered and used in the first-line diagnosis of patients with biological and clinical manifestations suggestive of HPS.

The potential utility of real-time PCR of the 16S-rRNA gene in the diagnosis of neonatal sepsis.

Istanbullu K, Köksal N, Çetinkaya M, Özkan H, Yakut T, Karkucak M, Dogan H. The potential utility of real-time PCR of the 16S-rRNA gene in the diagnosis of neonatal sepsis. Turk J Pediatr 2019; 61: 493-499. The purpose of this study was to evaluate the efficacy of real-time polymerase chain reaction (PCR) of the 16S rRNA gene in diagnosis of neonatal sepsis and compare it with conventional blood culture. A total of 150 infants were enrolled in this prospective study. The infants were classified into two groups: sepsis group (n=100) and control group (n=50). Blood samples for complete blood count, C-reactive protein, procalcitonin, serum-amyloid A, blood culture and PCR were obtained before initiating antibiotic treatment. Eight specific probes were used to perform PCR analysis for detection of 8 different microorganisms. The positivity rates of blood culture and PCR were found as 11% and 3%, respectively. The diagnosis of neonatal sepsis by PCR revealed a 16.6 % sensitivity, 97.8 % specificity, 33.3% positive predictive value and 94.8% negative predictive value compared with the blood culture. This study showed a low sensitivity of PCR of the 16S rRNA gene in the diagnosis of neonatal sepsis. This may be associated with the identification of rare microorganisms in the blood culture that were not included to PCR analysis. Implementation of all suspectible microorganisms into PCR assay may increase the sensitivity of 16S rRNA gene PCR in diagnosis of neonatal sepsis.

Investigation of MEFV gene polymorphisms (G138G and A165A) in adult patients with familial Mediterranean fever / Investigação de polimorfismos no gene MEFV (G138G e A165A) em pacientes adultos com febre mediterrânica familiar

Abstract Aim: Various mutations have been identified in the Mediterranean fever (MEFV) gene which is reported to be responsible from Familial Mediterranean fever (FMF). In our study, we aimed to determine the frequency of the MEFV mutations in our region and to investigate the impact of G138G (rs224224, c.414A>G) and A165A (rs224223, c.495C>A) gene polymorphisms on the clinical findings of the disease. Methods: One hundred and sixteen patients diagnosed with FMF and 95 control subjects were included in this study. We used the DNA sequence analysis method to identify the most prevailing 10 mutations located in exon 2 and 10 of MEFV gene. Results: As a result of the MEFV mutation analysis, the most common mutation was the M694V mutation allele with a frequency rate of 41.8%. When the patients group and control group were compared in terms of frequency of both polymorphic alleles (G polymorphic allele, observed in G138G and the A polymorphic allele, observed in A165A), the variation was observed to be statistically significant (p < 0.001). It was found that the MEFV mutation types have no relation with clinical findings and amyloidosis (p > 0.05). Conclusions: To our knowledge, our study is the first study in the Southern Marmara region that reports the frequency of MEFV mutations. Our findings imply that the polymorphisms of G138G and A165A may have an impact on progress of the disease. We think that more studies, having higher number of cases and investigating the polymorphisms of MEFV gene, are needed.

Resumo Objetivo: Identificaram-se mutações no gene da febre mediterrânica (MEFV) relatadas como responsáveis pela febre mediterrânica familiar (FMF). Este estudo teve como objetivo determinar a frequência de mutações no MEFV na região sul do mar de Mármara e investigar o impacto dos polimorfismos genéticos G138G (rs224224, c.414A > G) e A165A (rs224223, c.495C > A) nos achados clínicos da doença. Métodos: Foram incluídos neste estudo 116 pacientes com diagnóstico de FMF e 95 indivíduos no grupo controle. Usou-se o método de análise da sequência de DNA para identificar as 10 mutações mais prevalentes localizadas nos éxons 2 e 10 do gene MEFV. Resultados: Como resultado da análise da mutação MEFV, a mutação mais comum foi a mutação alélica M694 V, com uma taxa de frequência de 41,8%. Quando os grupos de pacientes e controles foram comparados em termos de frequência de ambos os alelos polimórficos (alelo polimórfico G, observado no G138G e o alelo polimórfico A, observado no A165A), a variação observada foi estatisticamente significativa (p < 0,001). Verificou-se que os tipos de mutação no MEFV não tinham relação com os achados clínicos nem com a amiloidose (p > 0,05). Conclusões: Que se tem conhecimento, este estudo é o primeiro feito na região sul do mar de Mármara que relata a frequência de mutações no MEFV. Os achados indicam que os polimorfismos G138G e A165A podem ter um impacto sobre o progresso da doença. Acredita-se que são necessários mais estudos que abranjam um maior número de casos e investiguem os polimorfismos do gene MEFV.

Investigation of MEFV gene polymorphisms (G138G and A165A) in adult patients with familial Mediterranean fever.

AIM: Various mutations have been identified in the Mediterranean fever (MEFV) gene which is reported to be responsible from Familial Mediterranean fever (FMF). In our study, we aimed to determine the frequency of the MEFV mutations in our region and to investigate the impact of G138G (rs224224, c.414A>G) and A165A (rs224223, c.495C>A) gene polymorphisms on the clinical findings of the disease. METHODS: One hundred and sixteen patients diagnosed with FMF and 95 control subjects were included in this study. We used the DNA sequence analysis method to identify the most prevailing 10 mutations located in exon 2 and 10 of MEFV gene. RESULTS: As a result of the MEFV mutation analysis, the most common mutation was the M694V mutation allele with a frequency rate of 41.8%. When the patients group and control group were compared in terms of frequency of both polymorphic alleles (G polymorphic allele, observed in G138G and the A polymorphic allele, observed in A165A), the variation was observed to be statistically significant (p<0.001). It was found that the MEFV mutation types have no relation with clinical findings and amyloidosis (p>0.05). CONCLUSIONS: To our knowledge, our study is the first study in the Southern Marmara region that reports the frequency of MEFV mutations. Our findings imply that the polymorphisms of G138G and A165A may have an impact on progress of the disease. We think that more studies, having higher number of cases and investigating the polymorphisms of MEFV gene, are needed.

Evaluation of TNF-alpha gene (G308A) and MBL2 gene codon 54 polymorphisms in Turkish patients with tuberculosis.

OBJECTIVE: MBL acts as a binding protein that enables uptake of mycobacteria into macrophages. And, TNF-alpha is an important cytokine that is involved in control of mycobacterial infections both in-vivo and in-vitro. A large number of genetic factors exerting susceptibility to tuberculosis has been identified, among which mannose-binding lectin and tumor necrosis factor-alpha call attention. The objective of this study is to compare the frequency of TNF-alpha and MBL gene polymorphisms between patients diagnosed with tuberculosis and healthy volunteers in Turkey, and determine the association between tuberculosis and TNF-alpha gene (G308A) and MBL2 gene codon 54 polymorphisms. MATERIAL AND METHODS: The study included 69 patients who were diagnosed with tuberculosis and 70 control subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect TNF-alpha (G308A) gene and MBL2 gene codon 54 polymorphisms. For statistical analysis, the significance level was determined as p<0.05. RESULTS: A comparison between patient and control groups in TNF-alpha (G308A) gene and MBL2 gene codon 54 polymorphisms showed no statistically significant difference (p>0.05). However, a comparison of mean body mass index (BMI) and smoking status showed a statistically significant difference between the tuberculosis and control groups (p=0.01 and p=0.009, respectively). CONCLUSION: Our results suggest that the MBL2 gene Codon 54 and TNF-alpha gene G308A polymorphisms are not associated with an increased risk for development of tuberculosis in our patients. Further studies are required including more cases of tuberculosis patients and other potentially relevant gene polymorphisms.

GSTT1 and GSTM1 gene polymorphisims in sarcoidosis.

INTRODUCTION: Sarcoidosis is a granulomatous disease of unknown cause, which affects all systems, especially the lungs and the lymphatic system. Genetic and environmental factors are held accountable for the etiology. Based on the general opinion, sarcoidosis develops after exposure to a specific environmental agent by genetically susceptible individuals.  The present study aimed to evaluate the disease susceptibility of the GSTT1 and GSTM1 gene polymorphisms in the patients with sarcoidosis. METHOD: The present study included 78 patients; 38 patients with histopathologically verified sarcoidosis and 40 control subjects. Multiplex PCR method was used to determine the GSTT1 and GSTM1 gene polymorphisms. The genotype was determined based on the bands formed in the agarose gel electrophoresis. The statistical analysis was done using the chi-square test. RESULTS: The positive/negative genotype rates were 79%/21% and 53%/47%, respectively in the case group for the GSTT1 and GSTM1 gene polymorphisms, whereas the positive/negative genotype rates were 77%/23% and 55%/45% in the control group. There was no statistically significant difference in the positive and negative genotypes compared with the case group and the control group for the GSTT1 and GSTM1 gene polymorphisms (p > 0.05). DISCUSSION: The results from the present study suggest that there is not any association with the control group for the disease susceptibility of the GSTT1 and GSTM1 gene polymorphisms in patients with sarcoidosis, and this result should be supported by large-scale studies because of the limited number of cases in the present study.

Distribution of KRAS and BRAF Mutations in Metastatic Colorectal Cancers in Turkish Patients.

The results of this study demonstrate the potential prognostic and predictive values of KRAS and BRAF gene mutations in patients with colorectal cancer (CRC). It has been proven that KRAS and BRAF mutations are predictive biomarkers for resistance to anti-EGFR monoclonal antibody treatment in patients with metastatic CRC (mCRC). We demonstrated the distribution of KRAS (codons 12, 13 and 61) and BRAF (codon 600) gene mutations in 50 mCRCs using direct sequencing and compared the results with clinicopathological data. KRAS and BRAF mutations were identified in 15 (30%) and 1 (2%) patients, respectively. We identified KRAS mutations in codon 12, 13 and 61 in 73.3% (11/15), 20% (3/15) and 6.67% (1/15) of the positive patients, respectively. The KRAS mutation frequency was significantly higher in tumors located in the ascending colon (p=0.043). Thus, we found that approximately 1/3 of the patients with mCRC had KRAS mutations and the only clinicopathological factor related to this mutation was tumor location. Future studies with larger patient groups should yield more accurate data regarding the molecular mechanism of CRC and the association between KRAS and BRAF mutations and clinicopathological features.

Glutathione S-Transferase M1 and T1 Gene Polymorphisms in Patients with Chronic Plaque-Type Psoriasis: A Case-Control Study.

OBJECTIVE: To determine the role of glutathione S-transferase (GST) isoenzyme polymorphisms as susceptibility factors in patients with psoriasis in a Turkish cohort. SUBJECTS AND METHODS: In this case-control study, 105 patients with plaque-type psoriasis and 102 healthy controls were recruited from the dermatology outpatient clinics of two university hospitals. Genomic DNA was extracted from whole blood using a DZ DNA isolation kit. Multiplex PCR was used to determine GSTM1 and GSTT1 polymorphisms in the isolated DNAs. RESULTS: Of the 150 patients with psoriasis, 83 (79%) were identified with the GSTT1 genotype and 22 (21%) with the null genotype. Of the 102 patients in the control group, 69 (67.6%) subjects were identified with the GSTT1 genotype and 33 (32.4%) with the null genotype. There was no significant difference between the patient and control groups (p = 0.063). Regarding the GSTM1 polymorphism, 54 (51.4%) patients were identified with this genotype and 51 (48.6%) with the null genotype; in the control group, 50 (49%) were identified with this genotype and 52 (51%) with the null genotype. Again there was no statistically significant difference between the groups (p = 0.957). CONCLUSION: In this Turkish cohort of patients with psoriasis, neither GSTT1 nor GSTM1 polymorphisms were associated with disease susceptibility. Larger studies with a wider range of GST isoenzyme are needed.

Qualitative and quantitative evaluation of the BCR-ABL fusion gene in chronic myelogenous leukemia by flourescence in situ hybridization and molecular genetic methods.

AIMS: Fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (QRT-PCR) were used to diagnose or screen for minimal residual disease (MRD) in Philadelphia (Ph) chromosome-positive leukemia. We compared the diagnostic utility of FISH and QRT-PCR at various time points in the course of chronic myelogenous leukemia (CML) and to determine the mean initial values for patients whose QRT-PCR results were not known at the time of diagnosis. RESULTS: We analyzed 135 results for 78 CML patients tested by FISH and QRT-PCR for the Ph chromosomal translocation. All newly diagnosed cases were positive by both methods. On follow-up following treatment, 1 case was FISH positive and QRT-PCR negative; 61 cases were FISH negative and QRT-PCR positive. Overall concordance was 54.1%. There was good concordance between QRT-PCR results and cytogenetic response categories. CONCLUSIONS: We confirmed that QRT-PCR allows precise measurement of low levels of BCR-ABL transcripts and can serve as a sensitive indicator of MRD. We also demonstrated 100% correlation between QRT-PCR and FISH in newly diagnosed CML.

Oxytocin system social function impacts in children with attention-deficit/hyperactivity disorder.

To investigate relationships between the polymorphisms and social functioning of children with Attention Deficit/Hyperactivity Disorder (ADHD), according to the polymorphism of three oxytocin receptor (OXTR) genes (rs53576, rs13316193, and and rs2268493). A total of 198 children-studying in the same primary and secondary school and matched in terms of age and gender (99 ADHD, 99 control)-were included in this study. The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version was administered to establish the clinical diagnosis. The Social Reciprocity Scale (SRS) was applied to evaluate social functioning. The total genomic DNA was isolated from buccal mucosa samples. No significant differences were determined between the ADHD and control groups in terms of rs2268493, rs13316193, and rs53576 genotype distribution (P = 0.078, P = 0.330, and P = 0.149, respectively). However, the control group T allele frequency in the OXTR Single Nucleotide Polymorphism (SNP) rs2268493 was significantly higher than the ADHD group (P = 0.024). Compared to the control group, the ADHD group had a higher score on the SRS scale (SRS total; Z = -21,135, P < 0.001). No significant difference existed in the SRS scale scores between the children with the T/T genotype and the C allele in the ADHD group (SRS total; Z = -0.543, P = 0.587). The allele distribution of the OXTR gene SNP rs2268493 was significantly different in the ADHD group, compared to the control group. This observation is important in understanding the underlying biological infrastructure in ADHD and developing treatment modalities.

Investigation of TNF-alpha gene (G308A) and GSTP1 gene (Ilel05Val) polymorphisms in Turkish patients with retinopathy of prematurity.

BACKGROUND/AIM: Retinopathy of prematurity (ROP) is one of the most frequent causes of blindness in newborn babies. Currently, its etiology is not fully understood.-In this study we aimed to investigate the correlation between a patient group with ROP and a control group in terms of the tumor necrosis factor-alpha (TNF-alpha) (G308A) gene and glutathione-S-transferase P1 (GSTP1) (Ilel05Val) gene polymorphism. MATERIALS AND METHODS: Sixty-two patients diagnosed with ROP and 58 control subjects were included in this study. For TNF-alpha (G308A) gene and GSTP1 (Ilel05Val) gene polymorphisms, the polymerase chain reaction-restriction fragment length polymorphism method was used. In statistical analysis the significance level was determined as P < 0.05. RESULTS: When the patient and control groups were compared in terms of TNF-alpha (G308A) gene and GSTP1 (Ilel05Val) gene polymorphisms, no statistically significant difference was found (P > 0.05). CONCLUSION: In our study, no correlation was identified between TNF-alpha (G308A) gene and GSTP1 (Ilel05Val) gene polymorphisms and susceptibility for development of ROP. Further studies are required with more cases of ROP patients and other gene polymorphisms that could be related.

Association between p16(CDKN2A) C540G polymorphism and tumor behavior in prolactinoma: A single-center study.

Pituitary tumors usually originate as benign sporadic adenomas and develop into invasive and aggressive tumors such as prolactinomas, which are common functioning pituitary adenomas. The aim of the present study was to examine the association between the tumor behavior in prolactinomas and the p16(CDKN2A) gene polymorphism occurring at the 3'-untranslated region of exon 3 (C540G). A total of 104 patients with prolactinoma were included and assigned to two groups based on invasive vs. non-invasive tumor behavior. Ki67 indices were recorded according to histopathology results. Genotypic analysis of the p16(CDKN2A) C540G polymorphism was carried out using a modified polymerase chain reaction-restriction fragment length polymorphism assay. The corresponding frequencies for CC, CG and GG genotypes in non-invasive vs. invasive tumors were 61.5, 30.8, 7.7 and 64.1, 28.2, 7.7%, respectively (not significant). The observed CG genotype frequency was higher compared with previous studies. In addition, the patients with giant adenomas or a high Ki67 index had a higher frequency of the CG genotype as compared with the other subgroups, although the differences were not significant (46.2 and 42.9%, respectively). In conclusion, a higher frequency of the C540G CG genotype of the CDKN2A gene was found among patients with prolactinoma in comparison with previous studies. These frequencies were also higher in the subgroups with elevated Ki67 or giant adenomas. Further studies are required to improve the definition of the role of the CG genotype in the development and progression of tumors in prolactinomas.

Does MBL2 codon 54 polymorphism play a role in the pathogenesis of psoriasis?

BACKGROUND: Psoriasis is a T cell-mediated immune disease in which various cytokines, primarily tumor necrosis factor-α (TNF-α), are complexly involved. Mannose-binding lectin (MBL) gene polymorphisms decrease MBL serum levels, thereby increasing the synthesis of proinflammatory cytokines such as TNF-α. OBJECTIVES: This trial was designed to evaluate the role of the MBL2 codon 54 polymorphism in the pathogenesis of psoriasis. METHODS: Fifty patients diagnosed with psoriasis vulgaris and 53 healthy subjects were included in the trial. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to determine the MBL2 codon 54 polymorphism. Genotypes were determined according to the bands formed in agarose electrophoresis gels. For the statistical analysis, the level of significance was set at P < 0.05. RESULTS: A total of 33 (66.0%) of the 50 psoriasis patients were detected to have A/A genotype and 17 (34.0%) had B/B genotype. Of the control subjects, 44 (83.0%) had A/A genotype and nine (17.0%) had B/B genotype. There was a statistically significant difference between the groups (P = 0.047). The analysis of allele frequencies revealed A allele prevalences to be 79 (79.0%) and 95 (89.6%), and B allele prevalences to be 21 (21.0%) and 11 (10.4%), in the patient and control groups, respectively. A statistically significant difference between allele frequencies was detected (P = 0.031). CONCLUSIONS: This study suggests that the MBL2 codon 54 polymorphism may have an association with psoriasis in the Turkish population.

Omentin serum levels and omentin gene Val109Asp polymorphism in patients with psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease of uncertain pathogenesis. Omentin is a new adipokine with anti-inflammatory properties; however, the relationship between psoriasis and omentin has not been fully established yet. OBJECTIVES: This study was designed to evaluate the relationship between psoriasis and omentin serum levels and Val109Asp polymorphism in exon 4 of the omentin gene. METHODS: Forty-nine patients with plaque-type psoriasis and 39 healthy subjects were included in the study. Omentin concentrations were determined by using enzyme-linked immunosorbent assay. Val109Asp polymorphism in exon 4 of the omentin gene was assessed by the polymerase chain reaction-restriction fragment length polymorphism method. Genotypes were determined according to the bands formed in agarose electrophoresis gels. In the statistical analysis, the level of significance was set at P < 0.05. RESULTS: The serum omentin levels of the patients with psoriasis (354.2 ± 152.0) were found to be significantly lower than those in the control group (488.7 ± 190.3) (P = 0.001). A moderate level negative correlation was determined between serum omentin level and body mass index and waist circumference. No significant differences were observed between the patient and control groups in terms of the genotype and allele frequency of Val109Asp polymorphism in exon 4 of the omentin gene (P > 0.05). CONCLUSIONS: Omentin serum levels were determined to be low in patients with psoriasis. No significant difference was found regarding Val109Asp polymorphism of the omentin gene. To the best of our knowledge, our study is the first clinical study to examine the relationship between psoriasis and omentin in terms of serum and genomic levels.

[The investigation of angiotensin converting enzyme I/D and plasminogen activator inhibitor-1 4G/5G polymorphisms in venous thromboembolism patients]. / Venöz tromboembolili hastalarda anjiyotensin dönüstürücü enzim I/D ve plazminojen aktivatör inhibitör-1 4G/5G gen polimorfizmlerinin arastirilmasi.

INTRODUCTION: Deep venous thrombosis and pulmonary embolism, known as venous thromboembolism and seen as a fairly common multifactorial diseases. Differ between populations due to genetic factors, several polymorphisms associated with venous thromboembolism was conducted. As a result of these studies the relationship between disease development and polymorphism is not clear yet. In this study we aimed to investigate the role of angiotensin converting enzyme insersion/deletion (ACE I/D) and plasminogen activator inhibitor-1 4G/5G (PAI-1 4G/5G) polymorphism in the development of disease. MATERIALS AND METHODS: In our study, DNA isolated from 80 venous thromboembolism patients and 79 control groups was used. While the classical polymerase chain reaction method used to investigate the ACE I/D polymorphism, the polymerase chain reaction based on allele-specific amplification was used for the detection of PAI-1 4G/5G polymorphism. RESULTS: As a result, there were no significant statistical differences for ACE I/D and PAI-1 4G/5G polymorphism among patient and control groups (p> 0.05). CONCLUSION: These findings revealed that there is no relationship between these polymorphisms and the development of venous thromboembolism, but large-scale studies are need to be done.

A polymorphism in ERAP1 is associated with susceptibility to ankylosing spondylitis in a Turkish population.

We assessed the role played by the ERAP1 gene in Turkish patients with ankylosing spondylitis (AS) in terms of disease susceptibility, clinical manifestations, and disease severity. We included 150 consecutive AS patients who met the modified New York classification criteria and 150 healthy controls. We documented the presence of 10 ERAP1 single-nucleotide polymorphisms (SNPs) and HLA-B27 in these patients. ERAP1 SNPs were genotyped using competitive allele-specific polymerase chain reaction. Differences between genotype and allele frequencies were compared using the Pearson's Chi-square test. The associations between ERAP1 SNPs, on the one hand, and with disease severity and clinical findings, on the other, were determined. One SNP, rs26653, was significantly associated with AS susceptibility (OR 1.609, 95% CI 1.163-2.226; p = 0.004). The population-attributable risk of possession of the rs26653 SNP allele was 23.4%. No relationship was noted between HLA-B27 positivity and the distribution of rs26653 genotype frequency. No associations were seen between disease severity measures and clinical manifestations of AS. In summary, an ERAP1 polymorphism was associated with AS in a Turkish population. The contributions of HLA-B27 and the rs26653 SNP to AS pathogenesis appear to be independent.

ACE gene I/D polymorphism and risk of sarcoidosis development in Turkish patients.

INTRODUCTION: Etiology of sarcoidosis is unknown but the prevalence of disease in different ethnic groups and identical twins, family characteristics indicate that genetic predisposition is a possible factor. The angiotensin-converting enzyme (ACE) has been implicated in the pahophysiology of sarcoidosis. The aim of this study is to investigate the influence of a polymorphism in I/D (Insertion/Deletion) of the ACE gene on the susceptibility to sarcoidosis. PATIENTS AND METHODS: Our study included 70 Turkish patients who had histopathological diagnosis of sarcoidosis and 69 healthy age and sex matched control subjects. Polymerase chain reaction was used for analysing an I/D polymorphism in the gene coding for ACE. Genotyping was done according to bands that were formed on the agarose gel electrophoresis. Chi-square test was used for statistical analysis and p< 0.05 was accepted as significance. RESULTS: Although the D allele was more frequent in the sarcoidosis patients group, the frequency of the D allele was 67% and 54% respectively in the sarcoidosis and the control group. No significant difference in allele frequencies of I/I, I/D, D/D polymorphisms was observed between the sarcoidosis and control group (p> 0.05). Similarly allele frequencies of I/I, I/D, D/D polymorphisms was not different between sarcoidosis patients with extrapulmonary involvement and sarcoidosis patients without extrapulmonary involvement (p> 0.05). CONCLUSION: Our findings have showed that contribution of ACE gene polymorphisms to susceptibility of disease development in Turkish sarcoidosis patients is not different from the healthy control subjects.

Effect of cyclin [corrected] D1 (CCND1) gene polymorphism on tumor formation and behavior in patients with prolactinoma.

The objective of this study was to investigate the effect of G870A gene polymorphism of CCND1 on the formation and behavioral features of prolactinomas. One hundred and thirteen patients with prolactinoma and 108 age and gender matched control were included in the study. The patients were divided into two groups as noninvasive and invasive tumors. CCND1 G870A gene polymorphism was compared in patients/control and invasive/noninvasive groups. A and G allele frequencies were found as 41.7% and 58.3% in the controls, and 61.1% and 38.9% in the patients (p<0.01). Rates of G/G, G/A and A/A genotypes were found as 11.8%, 55.9% and 32.4% in the noninvasive group, and 15.6%, 44.4% and 40.0% in the invasive group, respectively. Differences between patient and control groups were significant but were not between invasive and noninvasive groups in terms of the allele frequencies and genotype distribution. Mean tumor size and serum levels of prolactin at the time of diagnosis and change in these values after the treatment were not found statistically significant in genotype subgroups. CCND1 G870A gene polymorphism may be an important factor in the early stages of the tumor formation. However, it did not affect the features of the tumor.

Evaluation of the JAK2-V617F gene mutation in Turkish patients with essential thrombocythemia and polycythemia vera.

An activating mutation of Janus kinase 2 (JAK2-V617F) was previously described in chronic myeloproliferative disorders (MPD). In previously published studies, the frequency of the JAK2-V617F mutation was determined to be 80-90 % for patients with polycythemia vera (PV) and 40-70 % for essential thrombocythemia (ET). In this study, we analyzed the relationship between the JAK2-V617F mutation and clinical-hematological parameters in Turkish patients with MPD and compared these findings with published studies from other geographic regions. A total of 148 patients were studied; of which, 70 were diagnosed with PV and 78 with ET. The mutation status of JAK2 was determined using a tetra-primer polymerase chain reaction. We found that 80 % of the PV group and 42 % of the ET group were positive for the JAK2-V617F mutation. When all patients were analyzed, the levels of white blood cells, hemoglobin and splenomegaly were significantly different in patients with the JAK2-V617F mutation (p < 0.05). To our knowledge, this study is the first to evaluate the relationship between MPD and JAK2-V617F in Turkish patients. The JAK2-V617F mutation is frequently detected in the Turkish patients with MPD, and especially in patients with PV. Hence, it would be useful to include JAK2 mutation screening in the initial evaluation of patients suspected to have MPD.