[Show abstract][Hide abstract] ABSTRACT: Objective:
Gouty arthritis and familial Mediterranean fever (FMF) share some clinical and pathological features such as being classified as auto inflammatory disease, association with inflammasome, short-lived intermittent arthritis, and good response to colchicine and anti-interleukin-1 treatments. As Mediterranean fever (MEFV) gene is the causative factor of FMF, we aimed to investigate the prevalence of MEFV gene mutations and their effect on disease manifestations in Turkish gouty arthritis patients.
Ninety-seven patients diagnosed with primary gouty arthritis (93M and 4 F, 54 [37-84] years) and 100 healthy controls (94M and 6 F, 57 [37-86] years) included in the study. All subjects were genotyped for the MEFV variations. Number of gout attacks, diuretic use, and history of nephrolithiasis and presence of tophus were also recorded.
The carriage rate of MEFV mutations for patients and controls were 22.7% (n=22) and 24% (n=24) respectively. The comparison of the patient and control groups yielded no significant difference in terms of the MEFV mutations carriage rate (p=0.87). The allelic frequencies of the MEFV mutations in patients were 11.9% (n=23) and 14% (n=28) in controls (p=0.55). The presence of MEFV variants did not show any association with clinical features of gouty arthritis. The subgroup analysis of patients revealed that gouty arthritis patients with mutations had similar frequencies of tophus, history of nephrolithiasis and podogra compared to the ones without mutations (p>0.05).
This study does not provide support for a major role of MEFV mutations in Turkish gouty arthritis patients.
[Show abstract][Hide abstract] ABSTRACT: gouty arthritis and familial Mediterranean fever (FMF) share some clinical and pathological features such as being classified as auto inflammatory disease, association with inflammasome, short‐lived intermittent arthritis, and good response to colchicine and anti‐interleukin‐1 treatments. As Mediterranean fever (MEFV) gene is the causative factor of FMF, we aimed to investigate the prevalence of MEFV gene mutations and their effect on disease manifestations in Turkish gouty arthritis patients.Methodsninety‐seven patients diagnosed with primary gouty arthritis (93 M and 4 F, 54 [37‐84] years) and 100 healthy controls (94 M and 6 F, 57 [37‐86] years) included in the study. All subjects were genotyped for the MEFV variations. Number of gout attacks, diuretic use, and history of nephrolithiasis and presence of tophus were also recordedResultsthe carriage rate of MEFV mutations for patients and controls were 22.7% (n = 22) and 24% (n = 24) respectively. The comparison of the patient and control groups yielded no significant difference in terms of the MEFV mutations carriage rate (p = 0.87). The allelic frequencies of the MEFV mutations in patients were 11.9% (n = 23) and 14% (n = 28) in controls (p = 0.55). The presence of MEFV variants did not show any association with clinical features of gouty arthritis. The subgroup analysis of patients revealed that gouty arthritis patients with mutations had similar frequencies of tophus, history of nephrolithiasis and podogra compared to the ones without mutations (p > 0.05).Conclusionsthis study does not provide support for a major role of MEFV mutations in Turkish gouty arthritis patients.
Revista Brasileira de Reumatologia 11/2014; 68. DOI:10.1016/j.rbr.2014.10.008 · 1.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver-derived paraoxonase-1 (PON1) enzyme that is found in the circulation is bound to high-density lipoproteins and reduces the amount of oxidized lipids with its antioxidant effect. Humans have at least three different PON gene regions which are adjacent to the other on the 7th chromosome. It has been shown that PON1 gene and its polymorphisms are related with various diseases. It is also known that, hepatitis C virus (HCV) is tightly associated with the cell lipoproteins in each step of its replication cycle leading to modulation of the host lipid metabolism. The aim of this study was to investigate the relationship between the response to chronic hepatitis C (CHC) therapy and aminoacid changes in 55' and 192' regions of PON1 enzyme believed to be involved in the pathophysiology of many chronic diseases. A total of 49 CHC patients (27 male, 22 female; mean age: 52.9 ± 12.6 yrs), all infected with HCV genotype 1b and positive for anti-HCV and HCV-RNA were included in the study. Patients who were HCV-RNA negative at the sixth month following at least once pegilated interferon + ribavirin treatment, were considered as therapy-responders, whereas those who were HCV-RNA positive were considered as non-responders. The genomic DNAs were isolated from patients' blood samples in their routine follow-ups and Q/R192 and L/M55 PON1 polymorphism analysis in 55. and 192. regions was performed by T-ARMS-PCR (Tetra-primer amplification refractory mutation system-polymerase chain reaction) method. In our study, the analysis of PON1 polymorphisms yielded 44.1% of LL, 44.1% of LM and 11.8% of MM genotypes at position 55 and 55.9% of QQ, 41.2% of QR, and 2.9% of RR genotypes at position 192 in therapy-responders. In the evaluation of combined genotype analysis of the patients, there was only one case who was responsive to treatment with LL/RR genotype. Of the patients, eight harbored LL/QQ genotypes and seven of them (87.5%) were responsive to treatment. However, statistical analysis indicated that there was no relationship between PON1 L/M55 and PON Q/R192 polymorphisms and response to CHC treatment (chi-square test, p> 0.05). Our data did not support a relationship between PON1 polymorphisms and response to CHC therapy, in contrast to a few studies pointing out of this correlation. This might be attributed to relatively low number of patients included. In conclusion, since antiviral agents used for CHC therapy are limited and costly, it was thought that further investigations with large numbers of patients should be conducted to establish the presence of any relationship between the response to CHC therapy and genotypes of the PON1 enzyme.
[Show abstract][Hide abstract] ABSTRACT: Background:
In general, medical geneticists aim to pre-diagnose underlying syndromes based on facial features before performing cytological or molecular analyses where a genotype-phenotype interrelation is possible. However, determining correct genotype-phenotype interrelationships among many syndromes is tedious and labor-intensive, especially for extremely rare syndromes. Thus, a computer-aided system for pre-diagnosis can facilitate effective and efficient decision support, particularly when few similar cases are available, or in remote rural districts where diagnostic knowledge of syndromes is not readily available.
The proposed methodology, visual diagnostic decision support system (visual diagnostic DSS), employs machine learning (ML) algorithms and digital image processing techniques in a hybrid approach for automated diagnosis in medical genetics. This approach uses facial features in reference images of disorders to identify visual genotype-phenotype interrelationships. Our statistical method describes facial image data as principal component features and diagnoses syndromes using these features.
The proposed system was trained using a real dataset of previously published face images of subjects with syndromes, which provided accurate diagnostic information. The method was tested using a leave-one-out cross-validation scheme with 15 different syndromes, each of comprised 5-9 cases, i.e., 92 cases in total. An accuracy rate of 83% was achieved using this automated diagnosis technique, which was statistically significant (p<0.01). Furthermore, the sensitivity and specificity values were 0.857 and 0.870, respectively.
Our results show that the accurate classification of syndromes is feasible using ML techniques. Thus, a large number of syndromes with characteristic facial anomaly patterns could be diagnosed with similar diagnostic DSSs to that described in the present study, i.e., visual diagnostic DSS, thereby demonstrating the benefits of using hybrid image processing and ML-based computer-aided diagnostics for identifying facial phenotypes.
Artificial Intelligence in Medicine 08/2014; 62(2). DOI:10.1016/j.artmed.2014.08.003 · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Although genetic factors known to play crucial role in the pathogenesis of ankylosing spondylitis (AS), little is known about the molecular mechanisms that are responsible. In that context, endoplasmic reticulum aminopeptidase 1 (ERAP1) gene has been suggested as the most important factor in genetic susceptibility, with the exception of HLA-B27.
Objectives To investigate the role of ERAP1 in the pathogenesis of AS and its relationship with clinical findings.
Methods We included 150 consecutive AS patients who were fulfilling the Modified New York classification criteria and 150 blood donors as healthy control. DNA isolation from the participants’ blood samples was performed automatically by the BioRobot® EZ1 station and we investigated the presence of ERAP1 gene single nucleotide polymorphisms (SNPs) (rs30187, rs27044, rs26653, rs27037, rs2287987, rs10050860, rs17482078, rs7711564, rs27980, rs27529) by using the method of competitive allele-specific PCR. We also determined the subgroups of HLA-B27 by PCR-Sequence Specific Primer (SSP). The differences between genotype and allele frequencies were compared by Pearson Chi-square test.
Results The mean age of patients and controls were 34.6 and 29.4 years, respectively. In the patient group, the rate of HLA-B27 positivity was 66.7%, while this was 4.7% in the control group. We detected rs26653 SNP C/C homozygotes in 36 patients (24.0%) and 21 controls (14.0%). The frequency distribution of rs26653 SNP C/C homozygous genotype between the groups was found to be statistically significant (p=0.015). We identified that the frequency of rs26653 SNP’s risky C allele was higher in the patient group (50.0%) than the control group (38.3%) (OR 1.609, %95 CI 1.163-2.226, p=0.004). The contribution of rs26653 SNP’s risky C allele to the total AS genetic risk was calculated as 23.4%. The differences between genotype and allele frequency distribution of other SNPs were not statistically significant.
Conclusions In our study, only rs26653 SNP, out of 10 ERAP1 gene SNPs, which were suggested as genetic susceptibility factors in AS at previous studies, was found to be associated with the risk of genetic predisposition in our AS group. The contribution of rs26653 SNP to the total AS genetic risk in the present study was found as 23.4% and it was compatible with the literature (26%). Since there was no relation between HLA-B27 positivity and rs26653 SNP, the contribution of both factor to the pathogenesis of AS seems to be independent from each other.
Disclosure of Interest None Declared
Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A283-A283. DOI:10.1136/annrheumdis-2013-eular.879 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic arthritis of familial Mediterranean fever (FMF) involves weight-bearing joints and can occur in patients without a history of acute attack. Our aim was to investigate a possible causal relationship between FMF and osteoarthritis in a population in which FMF is quite common.
Patients with late stage primary osteoarthritis were enrolled, and five MEFV gene mutations were investigated. The frequency of MEFV gene mutations was compared among patients with osteoarthritis and a previous healthy group from our center.
One hundred patients with primary osteoarthritis and 100 healthy controls were studied. The frequency of MEFV gene mutations was significantly lower in the osteoarthritis group (9% vs. 19%). M694V was the most frequent mutation (5%) in the osteoarthritis group, whereas in the control group, E148Q was the most common (16%). In subgroup analyses, the mutation frequency of patients with hip osteoarthritis was not different from that of patients with knee osteoarthritis and controls (7.1%, 9.7%, and 19%, respectively). There were no differences among the three groups with respect to MEFV gene mutations other than E148Q (8.1% vs. 3.6%). E148Q was significantly lower in the osteoarthritis group than in the controls (16% vs. 1%), although the mutations did not differ between patients with knee osteoarthritis and controls.
In a population with a high prevalence of MEFV gene mutations, we did not find an increased mutation rate in patients with primary osteoarthritis. Furthermore, we found that some mutations were significantly less frequent in patients with osteoarthritis. Although the number of patients studied was insufficient to claim that E148Q gene mutation protects against osteoarthritis, the potential of this gene merits further investigation.
The Korean Journal of Internal Medicine 09/2013; 28(5):594-8. DOI:10.3904/kjim.2013.28.5.594 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Rheumatology International 07/2013; 33(11). DOI:10.1007/s00296-013-2824-y · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
Tuberkuloz ve toraks 06/2013; 61(2):88-95. DOI:10.5578/tt.5185
[Show abstract][Hide abstract] ABSTRACT: The study investigated whether travelling after amniocentesis has an effect on outcomes of the procedure. A total of 57 patients who were referred to our tertiary centre from distant cities and who had to travel back by bus, by car or by plane, were evaluated for amniocentesis outcomes. The travelled distances were divided into 3 zones, which consisted of 50-100, 101-300 and over 300 km. Patients (n = 85) residing in our city (within 50 km) were identified as the control group. All of the procedures were done by the same perinatology team, following exactly the same procedure. It was found that there was one transient amniotic fluid leakage patient who had travelled 70 km by car after the amniocentesis. No other patients who had to travel after amniocentesis had a complication related to the procedure. It was concluded that although done on a limited number of patients, this study provides the first scientifically supported evidence that travelling by bus, by car or by plane after amniocentesis does not have adverse effects on the outcomes.
Journal of Obstetrics and Gynaecology 05/2013; 33(4):343-5. DOI:10.3109/01443615.2013.767784 · 0.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The coincidence of trisomy 21 and a structural rearrangement is very rare, and even it has not been reported as a prenatal diagnosis yet. In this article, we present an autosomal translocation carrier fetus with trisomy 21: 47,XX,+21, t(3;8)(p21;q24). Although the coincidence of reciprocal translocation and trisomy may be seen in reciprocal translocation carrier families, de novo cases are extremely rare. The presented case is diagnosed by amniocentesis, which was performed because of abnormal fetal ultrasonographic findings and increased trisomy 21 risk at maternal serum screening test. The postmortem pathologic examination of the fetus revealed that the findings of hypertelorism and right lung with two lobes are interesting novel findings of our cases associated with the breakpoints 3p21 and 8q24.
[Show abstract][Hide abstract] ABSTRACT: In the clinical diagnosis of facial dysmorphology, geneticists attempt to identify the underlying syndromes by associating facial features before cyto or molecular techniques are explored. Specifying genotype-phenotype correlations correctly among many syndromes is labor intensive especially for very rare diseases. The use of a computer based prediagnosis system can offer effective decision support particularly when only very few previous examples exist or in a remote environment where expert knowledge is not readily accessible. In this work we develop and demonstrate that accurate classification of dysmorphic faces is feasible by image processing of two dimensional face images. We test the proposed system on real patient image data by constructing a dataset of dysmorphic faces published in scholarly journals, hence having accurate diagnostic information about the syndrome. Our statistical methodology represents facial image data in terms of principal component analysis (PCA) and a leave one out evaluation scheme to quantify accuracy. The methodology has been tested with 15 syndromes including 75 cases, 5 examples per syndrome. A diagnosis success rate of 79% has been established. It can be concluded that a great number of syndromes indicating a characteristic pattern of facial anomalies can be typically diagnosed by employing computer-assisted machine learning algorithms since a face develops under the influence of many genes, particularly the genes causing syndromes.
Machine Learning and Applications (ICMLA), 2012 11th International Conference on; 01/2012
[Show abstract][Hide abstract] ABSTRACT: Ring chromosome 21 syndrome is a rare clinical condition. Most of the patients have a recognizable phenotype and multisystem involvement is described. Structural neurologic anomalies have also been described, but waddling gait due to lower motor neuron involvement has not been previously reported in association with ring 21.
Brain & development 12/2011; 34(9):792-5. DOI:10.1016/j.braindev.2011.12.003 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: In the present study, we aimed to determine a possible association of specific polymorphisms of IL-1 beta genes with enhanced production of IL-1 beta in patients with idiopathic hypogonadotropic hypogonadism (IHH). Material and Methods: Forty-five male IHH patients who had no familial relationship with each other and 58 ethnically matched healthy male controls were enrolled in the study. Patients were diagnosed with IHH according to failure in spontaneus puberty and decreased serum testosterone concentration below normal range for adults. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were low or in normal range in patients with IHH. In this study, we analyzed the gene polymorphisms of IL-1 beta at positions -511 and +3953 and serum IL-1 beta levels in patients with IHH and control subjects. For this purpose, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and enzyme-linked immunosorbent assay (ELISA) methods. Results: The frequency of genotype 2/2 of IL-1 beta-511 gene was significantly higher in patients with IHH compared to healthy control subjects (24.4% vs 8.6%, respectively, p= 0.019). Although there was no significant difference in serum concentrations of IL-1 beta between total patients with IHH and healthy controls, the levels in the patients with the 1/2 genotype of IL-1 beta-511 and with the 2/2 genotype of IL-1 beta-511 were found significantly higher than the levels of patients with the 1/1 genotype of IL-1 beta-511. Conclusion: Our results indicate that IL-1 beta-511 gene polimorphism may be the cause of increased IL-1 beta production in patients with IHH.
Turkiye Klinikleri Journal of Medical Sciences 12/2010; 30(6):1814-1819. DOI:10.5336/medsci.2009-14707 · 0.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the rate of MEFV gene mutations, the gene responsible for familial Mediterranean fever (FMF), in patients with hematolymphoid neoplasm. The rate of the five most common MEFV gene mutations (M694V, M680I, V726A, M694I and E148Q) was determined in 46 patients with hematolymphoid neoplasm. We found a high frequency of carriers in patients with multiple myeloma (60%) and acute lymphocytic leukaemia (33.3%), whereas patients with chronic lymphocytic leukaemia (9%) and non-Hodgkin lymphoma (5%) had a low mutation carrier rate. There is no MEFV gene mutation in patients with Hodgkin lymphoma. Furthermore, the statistically significant predominance of strong heterozygous mutations such as M694V and M680I in patients with hematolymphoid neoplasm; none had own and/or family history compatible with FMF, is interesting. In conclusion, we found a high frequency of carriers for MEFV gene in patients with multiple myeloma and acute lymphocytic leukaemia. The data of our study may provide some new insights in understanding of individual genetic differences in susceptibility to these neoplasms.
International Journal of Immunogenetics 10/2010; 37(5):387-91. DOI:10.1111/j.1744-313X.2010.00938.x · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to investigate the rate of MEFV, the gene mutated in familial Mediterranean fever, mutations in patients with myeloid neoplasm and to determine if known mutations of MEFV cause a tendency for myeloid neoplasms. The frequency of the five most common MEFV gene mutations (M694V, M680I, V726A, E148Q and M694I) was determined in 26 patients with myeloid neoplasm. We identified 1 homozygous (E148Q/E148Q), 1 compound heterozygous (M694V/E148Q) and 5 heterozygous MEFV gene mutations; none had their own and/or family history compatible with familial Mediterranean fever. The mean overall mutation rate was 0.269. We found a high frequency of carriers in patients with myelodysplastic syndrome (66.6%), polycythemia vera (33.3%) and acute myeloid leukemia (28.6%). However, there was no MEFV gene mutation in patients with chronic myeloid leukemia. In conclusion, this study reports for the first time a possibly high prevalence of MEFV gene mutations in patients with myeloid neoplasm, especially myelodysplastic syndrome, polycythemia vera and acute myeloid leukemia. Our findings could open new perspectives for MEFV gene mutations in myeloid neoplasms and its association with tumor promotion. Further research is needed to determine the actual role of MEFV gene mutations in these malignancies.
International journal of hematology 06/2010; 91(5):758-61. DOI:10.1007/s12185-010-0577-x · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Disorder of sexual development is characterized with phenotypic-genotypic incompatibility and most of the cases result from the failure of steroid biosynthesis pathway. In this article genetic analysis results of 66 cases who were admitted to our department with disorders of sexual development diagnosed with clinical, laboratory and radiological findings since 2000 are presented. Of all the cases, 10 (15.15%), 15 (22.72%) and 41 (62.12%) presented in the newborn, childhood and adult periods, respectively. Educational and economical status of the families of the cases presenting in the neonatal period were better than those of the cases presenting in adult period. Approximately one third of families with disorders of sexual development had consanguineous marriages. In this selected series of 66 cases, 16 cases (24.24%), 5 cases (13.20%), 2 cases (3.03%) and 43 cases (65.15%) had female pseudohermaphroditism, male pseudohermaphroditism, true hermaphroditism and gonadal dysgenesis, respectively. SRY gene region on Y chromosome was positive in all of the cases with male phenotype consistent ultrasonographically whereas it was negative in all of the cases with female phenotype consistent ultrasonographically. Disorders of sexual development are a medical and social problem, and early diagnosis depends on the education of the whole population. The diagnosis of disorders of sexual development is only possible through the establishment of phenotypic and genotypic association.