The investigation of association between IL-1Ra and ACE I/D polymorphisms in carpal tunnel syndrome

WOS: 000423046100052PubMed ID: 28370589BackgroundCarpal tunnel syndrome (CTS) is a common neurologic impairment caused by injury on the median nerve in the wrist, characterized by pain and loss of sensory. CTS usually occurs through three factors, such as a mechanical pressure on median nerve, immunologic changes, and oxidative stress. The aim of this study was to evaluate the influence of interleukin-1 receptor antagonist (IL-1Ra) and angiotensin-converting enzyme (ACE) I/D polymorphisms on the susceptibility of patients to the CTS. MethodsOne hundred fifty-eight patients with CTS and 151 healthy controls were enrolled in this study. Each patient was analyzed according to diseases symptoms, such as gender, a positive Tinel's sign, a positive Phalen maneuver, disease sides, EMG findings, and clinical stage. We applied the polymerase chain reaction (PCR) to determine the polymorphisms of IL-1Ra and ACE I/D. ResultsThe statistically significant relation was not found between IL-1Ra, ACE I/D polymorphisms and CTS (respectively, P>.05; P>.05, OR: 1.51, CI: 0.82-1.61). Additionally, in the result of the statistical analysis compared with gene polymorphisms and clinical characteristics, we did not find any correlation (P>.05). ConclusionsOur findings showed that there are no associations of IL-1Ra and ACE I/D polymorphisms with susceptibility of a person for the development of CTS. So, it means that these polymorphisms do not create a risk for the development of CTS. Further studies with larger populations will be required to confirm these findings in different study populations

Mutational Spectrum of the MEFV Gene in AA Amyloidosis Associated With Familial Mediterranean Fever

WOS: 000382833300002PubMed ID: 27225717Introduction. Familial Mediterranean fever (FMF) is a recessively inherited disease which is characterized by recurrent episodic fever, abdominal pain, and polyserositis. It is caused by mutations in the MEFV gene, encoding the pyrin protein. The most important complication of FMF is secondary (AA) amyloidosis that leads to kidney failure. This study aimed to identify the frequency and distribution of MEFV mutations in Turkish patients with FMF-associated AA amyloidosis. Materials and Methods. A total of 57 patients with FMF-associated AA amyloidosis and 60 healthy controls were included in this study. We analyzed the MEFV gene for E148Q, M694V, M680I, and V726A mutations and R202Q variant by polymerase chain reaction and restriction fragment length polymorphism methods. Results. The male-female ratio was 0.72. The mean age of the patients was 29.8 +/- 12.8 years. Among the patients, the rate of the MEFV mutations was found to be 77.2%. The most frequently observed genotype was homozygous M694V mutation, which was present in 17 patients (29.8%, P <.001), followed by compound heterozygous M680I/ M694V (14.3%, P =.01). The R202Q allele frequencies were significantly different between patients and control group (P =.02; odds ratio, 0.53; 95% confidence interval, 0.30 to 0.94). Conclusions. In this study, mutation analysis of MEFV gene confirmed that the most frequent mutation was homozygous M694V genotype. R202Q may be important in patients with FMF-associated AA amyloidosis. Thus, it is suggested that investigation of R202Q should be considered as a genetic test for Turkish FMF patients

Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

Background Major depressive disorder (MDD) is a complex disease and a significant health problem that is prevalent across the world. Angiotensin-converting enzyme (ACE) has an important role in renin-angiotensin system (RAS) and converts inactive angiotensin I to a potent vasopressor and aldosterone-stimulating peptide angiotensin II. Levels of ACE in plasma vary according to the insertion/deletion (I/D) polymorphism of ACE gene. Objective The aim of the current study was to examine the influence ACE gene I/D variations on the risk of MDD. Methods In the present case-control study, we analyzed ACE I/D polymorphism in 346 MDD patients and 210 healthy subjects using polymerase chain reaction technique. Results Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the I/D polymorphism of ACE gene. Discussion Our findings suggest that the ACE I/D polymorphism is not associated with MDD in Turkish case-control study. Further studies are still needed

In Silico Analysis of FMR1 Gene Missense SNPs

WOS: 000377830900004PubMed ID: 26880065The FMR1 gene, a member of the fragile X-related gene family, is responsible for fragile X syndrome (FXS). Missense single-nucleotide polymorphisms (SNPs) are responsible for many complex diseases. The effect of FMR1 gene missense SNPs is unknown. The aim of this study, using in silico techniques, was to analyze all known missense mutations that can affect the functionality of the FMR1 gene, leading to mental retardation (MR) and FXS. Data on the human FMR1 gene were collected from the Ensembl database (release 81), National Centre for Biological Information dbSNP Short Genetic Variations database, 1000 Genomes Browser, and NHLBI Exome Sequencing Project Exome Variant Server. In silico analysis was then performed. One hundred-twenty different missense SNPs of the FMR1 gene were determined. Of these, 11.66 % of the FMR1 gene missense SNPs were in highly conserved domains, and 83.33 % were in domains with high variety. The results of the in silico prediction analysis showed that 31.66 % of the FMR1 gene SNPs were disease related and that 50 % of SNPs had a pathogenic effect. The results of the structural and functional analysis revealed that although the R138Q mutation did not seem to have a damaging effect on the protein, the G266E and I304N SNPs appeared to disturb the interaction between the domains and affect the function of the protein. This is the first study to analyze all missense SNPs of the FMR1 gene. The results indicate the applicability of a bioinformatics approach to FXS and other FMR1-related diseases. I think that the analysis of FMR1 gene missense SNPs using bioinformatics methods would help diagnosis of FXS and other FMR1-related diseases

The Effect of IL-4 Gene Polymorphism in Carpal Tunnel Syndrome

WOS: 000376567100013Aim: Carpal tunnel syndrome (CTS) is a neurological disorder characterized by paresthesia and pain in the hands due to lesions and /or dysfunction of the median nerve at the wrist. The exact pathogenesis of CTS is not clear. Genetic factors may play a role in CTS susceptibility. Biochemical mediators such as cytokines may have a role in carpal tunnel mediated neuropathy. The aim of the present study was to analyse the association of IL-4 VNTR polymorphism with CTS susceptibility and disease progression in patients with CTS in a Turkish population. Material and Method: The study included 155 patients with CTS and 140 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) for the IL-4 gene 70 bp VNTR polymorphisms. Results: There was no statistically significant difference between the groups with respect to IL-4 genotype distribution (p>0.05). The P1 allele was significantly higher in CTS patients than in healthy controls (p 0.05). Discussion: Our findings indicate that the IL-4 70 bp VNTR polymorphism is not a relevant CTS marker and that the P1 allele may be related to CTS in a Turkish population. Further research with larger patient populations is necessary to ascertain the implications of IL-4 and anti-inflammatory cytokines polymorphisms in CTS

Karpal Tünel Sendromunda IL-4 Gen Polimorfizminin Etkisi

Amaç: Karpal tünel sendromu el bileğinde medyan sinirin disfonksiyonu ve/veya lezyonları nedeniyle elde uyuşma ve ağrı ile karakterize nörolojik bir hastalıktır. KTS'nin patogenezi tam olarak açık olmamakla birlikte, genetik faktörler KTS'ye yatkınlıkta rol oynayabilmektedir. Sitokinler gibi biyokimyasal faktörler KTS'nin neden olduğu nöropatide rol alabilmektedir. Bu çalışmanın amacı bir Türk populasyonunda KTS yatkınlığı ile IL-4 VNTR polimorfizmi arasındaki ilişkileri ve IL-4 VNTR polimorfizminin KTS'li hastalarda hastalığın gelişimi üzerine etkilerini incelemektir. Gereç ve Yntem: Çalışmaya KTS'li 155 hasta ve 140 sağlıklı kontrol dâhil edilmiştir. Hasta ve kontrollerin genomik DNA'lar izole edilmiş ve IL-4 geni 70 bç'lik VNTR polimorfizmleri polimeraz zincir reaksiyonu kullanılarak genotiplenmiştir. Bulgular: Hasta ve kontrol grupları arasında IL-4 genotip dağılımı açısından istatistiksel olarak anlamlı bir fark bulunmamaktadır (p>0.05). Ancak, P1 allelinin KTS'li hastalarda sağlıklı kontrollere göre anlamlı derecede fazla olduğu saptanmıştır (p0.05). The P1 allele was significantly higher in CTS patients than in healthy controls (p0.05). Discussion: Our findings indicate that the IL-4 70 bp VNTR polymorphism is not a relevant CTS marker and that the P1 allele may be related to CTS in a Turkish population. Further research with larger patient populations is necessary to ascertain the implications of IL-4 and anti-inflammatory cytokines polymorphisms in CTS

Effects of subtelomeric copy number variations in miscarriages

WOS: 000369949900008PubMed ID: 26291815Purpose: This study was performed on miscarriage samples for chromosome analysis to detect copy number variations (CNVs) related to subtelomeric regions, and with these results we aimed to adapt multiplex ligation-dependent probe amplification (MLPA) method for prenatal diagnosis. Materials and methods: The cell cultures and DNA isolations were performed on 60 miscarriage samples. For maternal contamination analysis, DNA isolations and quantitative fluorescent polymerase chain reactions were done using peripheric blood of mothers who had miscarriages. We compared short tandem repeat peak profiles of miscarriage samples and mothers. The subtelomeric regions of the chromosomes were assessed using the MLPA method. Results: Of 43 miscarriage samples, 19 had normal karyotype (44.2%), 10 had numerical abnormalities (23.3%), and 2 had structural abnormalities (4.7%). Subtelomeric 16q duplication was determined in 2 of the 30 miscarriage samples investigated with MLPA method (6.6%). Conclusion: There is no statistically significant difference between two groups (p > 0.05). However, the fact that the 6.6% subtelomeric CNV found in miscarriage samples was not found in controls, showed that further studies are required. We recommend that the miscarriage samples of the couples with recurrent miscarriage should be analyzed in terms of subtelomeric CNV after the exclusion of other clinical reasons.Ondokuz Mayis University Research FoundationOndokuz Mayis University [PYO.TIP.10043]The authors declare no conflict of interest. This study was supported by Ondokuz Mayis University Research Foundation (PYO.TIP.10043)

Genotoxic Effects of Prenatal Exposure to Levetiracetam During Pregnancy on Rat Offsprings

WOS: 000348134300013PubMed ID: 25600534Levetiracetam is a new-generation antiepileptic drug initially approved as an adjunctive treatment for patients with refractory partial seizures and is now also used as a monotherapy. The aim of this study was to evaluate the genotoxic effects of levetiracetam exposure during pregnancy on rat offsprings. In this study, we used the newborn pups of rats exposed to levetiracetam during pregnancy. Thirty Sprague-Dawley rats were divided into three groups. The mother rats of groups 1 and 2 were treated with different doses of levetiracetam (25 mg/kg/d and 50 mg/kg/d) from gestational days 1 to 18 during pregnancy. Group 3 (control group) was not treated with any drug. In vivo sister chromatid exchange (SCE) induction and in vivo micronucleus formation were assessed. Bone marrow from rat pups were used for investigation. As a result of this study, levetiracetam exposure did not alter SCE frequencies or the mean of number of micronuclei in the prenatal period (p>0.05). Levetiracetam did not cause miscarriage during pregnancy in mother rats. The present study highlighted fetal safety after prenatal exposure to levetiracetam.Ondokuz Mayis University BAPOndokuz Mayis University [PYO-TIP-1901.11]We would like to thank Ondokuz Mayis University BAP for supporting our project (PYO-TIP-1901.11)

Evaluation of apoptotic cell death on liver and kidney tissues following administration of levetiracetam during prenatal period

WOS: 000389666700009PubMed ID: 27255296Objective: Levetiracetam is a new generation antiepileptic drug used in treatment of patients with epilepsy and has adverse effects on different tissues. We aimed to evaluate the apoptotic effects of levetiracetam exposure during pregnancy on liver and kidney tissues of rat pups. Methods: We analyzed the newborn rat pups exposed to levetiracetam during prenatal period. Fifteen pregnant female rats were divided into three groups. The group 1 and 2 rats were treated with different doses of levetiracetam (25 mg/kg/d and 50 mg/kg/d, respectively) from gestational days 1-22 during pregnancy. Group 3 (control group) was treated with the same volume of saline. Apoptosis was evaluated by the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) method. Liver and kidney tissues from rat pups were used for investigation. Results: The percent of TUNEL positive apoptotic cells in group 1 were 22 and 17.5 for kidney and liver, respectively. The percent of TUNEL positive apoptotic cells in group 2 were 20.9 and 20.9 for kidney and liver, respectively. The percent of TUNEL positive apoptotic cells in group 3 were 18.4 and 17.1, respectively, for kidney and liver. The apoptotic index was the same in kidney and liver tissues of all groups. Conclusion: Our results demonstrate that the prenatal exposure of levetiracetam has no apoptotic effects on liver and kidney of rat pups and, it has biosafety in pregnancy in terms of apoptosis. The first study evaluating the apoptotic effects on liver and kidney tissues following administration of levetiracetam during prenatal period.Ahi Evran University Research Foundation [SYO.E1.16.001]This study was supported by Ahi Evran University Research Foundation (SYO.E1.16.001)