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

Distribution of the 23-bp polymorphism of the prion protein gene in Jersey cattles in Turkey

Background: Bovine spongiform encephalopathy (BSE) is a prion disease that is always fatal in cattle and is considered an important risk factor for human health. Genetic polymorphisms that alter prion proteins may be associated with susceptibility or resistance to infectious spongiform encephalopathy. Therefore, we investigated the distribution of the 23 bp indel variant in the prion protein (PRNP) gene in Jersey cattle in Turkey. Methods: A total of 95 unrelated Jersey cattle (79 of reproductive age and 16 of non-reproductive age) from a private farm in Izmir were included in the study. Genomic DNA was obtained from the milk of reproductive-age cattle and the saliva of non-reproductive-age cattle. A 23-bp indel polymorphism in the PRNP gene promoter region was genotyped by polymerase chain reaction (PCR) analysis. Results: The three genotypes of the PRNP 23-bp indel variant were classified as follows: (223 bp), I/D (both 223 and 200 bp fragments), and D/D (200 bp). The frequencies of the I/I, I/D, and D/D genotypes of the PRNP 23-bp indel variant in cattle were 22 (23.16%), 48 (50.53%), and 25 (26.32%). We then examined genotype and allele distribution according to service period. No significant difference was detected in terms of PRNP gene 23 bp-indel variant genotype and allele distribution in the groups created according to the service period (p&gt;0.05). Conclusion: Although the PRNP gene 23 bp-indel variant genotype and allele distribution in jersey-type cattle in Turkey did not differ according to service period,  our results may benefit the understanding of the genetic characteristics of the PRNP gene in cattle breeds

Interleukin-1Ra rs2234663 and Interleukin-4 rs79071878 Polymorphisms in Familial Mediterranean Fever

WOS: 000372761300010PubMed ID: 26861613Objective: Familial Mediterranean Fever (FMF) is an autosomal recessively inherited auto inflammatory disorder. MEFV gene, causing FMF, encodes pyrin that is associated with the interleukin-1 (IL-1) related inflammation cascade. The aim of this study was to investigate the relationship of interleukin-1 receptor antagonist (IL-1Ra) and interleukin-4 (IL-4) polymorphisms with the risk of FMF in the Turkish population. Methods: This study included 160 patients with FMF (74 men, 86 women) and 120 healthy controls (50 men, 70 women), respectively. Genotyping of IL-1Ra rs2234663 polymorphism was evaluated by gel electrophoresis after polymerase chain reaction (PCR). The IL-4 rs79071878 polymorphism was determined by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis. The results of analyses were evaluated for statistical significance. Results: There was no significant difference in IL-1Ra genotype and allele distributions between FMF and the control groups (p > 0.05). However, a significant association was observed between FMF patients and control groups according to IL-4 genotype distribution (p = 0.016), but no association was found in the allelic frequency of IL-4 between FMF patients and the controls (p > 0.05, OR: 1.131, Cl 95%: 0.71-1.81). Conclusions: The IL-4 rs79071878 polymorphism, was associated whereas the IL-1Ra rs2234663 polymorphism was not associated with FMF risk in the Turkish population. Larger studies with different ethnicities are needed to determine the impact of IL-1Ra and IL-4 polymorphism on the risk of developing FMF. (C) 2016 Elsevier B.V. All rights reserved

The importance of MTHFR C677T/A1298C combined polymorphisms in pulmonary embolism in Turkish population

Background and objective: Pulmonary embolism (PE) is an important cardiovascular emergency with high mortality. There are still problems related to the diagnosis of PE and genetic research may play a key role on diagnosis as well as determining risk stratification. In the present study, the aim was to evaluate MTHFR C677T and A1298C polymorphisms that play a role on folate metabolism in PE patients. Materials and methods: A total of 118 PE patients and 126 controls were enrolled in the current study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses for the MTHFR C677T and A1298C polymorphisms. Results: There was no association between clinical and demographic characteristics of PE patients and both MTHFR C677T and A1298C polymorphisms. Allele frequencies showed a significant difference between patients and controls. T allele frequency was significantly higher in the patients\u27 group than the control group. There was an association between PE and combined MTHFR C677T and A1298C polymorphisms. Conclusion: We found an association between MTHFR C677T/A1298C combined mutations and PE in the Turkish population. Future genetic studies investigating combined mutations could be very helpful to identify risk population in PE

Has High-Frequency Oscillation Technique Any Benefit to Prevent Pulmonary Complications in Abdominal Surgery Patients?

Objective: Postoperative patients requiring intensive care are at risk of developing pneumonia and clearance of secretions may be difficult because of the type of surgery and pain. Enhanced mucociliary clearance with high-frequency chest wall oscillation (HFCWO) therapy devices were previously used in chronic obstructive pulmonary disease and thoracic surgery patients. We studied the short-term effects of HFCWO on postoperative abdominal surgery patients

Angiotensin Converting Enzyme Gene Insertion/Deletion Variant and Familial Mediterranean Fever-related Amyloidosis

WOS: 000435148300003PubMed ID: 29891744Introduction. The most important complication of familial Mediterranean fever (FMF) is secondary amyloidosis, which can lead to kidney failure. Genetic variability in the genes of various components of the renin-angiotensin system may play a role in the pathogenesis of the kidney disorders. The aim of the present study was to investigate the association between angiotensin converting enzyme (ACE) gene I/D variant and risk of developing FMF-related amyloidosis in Turkish patients. Materials and Methods. A total of 240 individuals consisting of 40 patients with FMF-related amyloidosis, 100 FMF patients without amyloidosis, and 100 healthy controls were recruited. For all of the participants, ACE I/D variant was detected by the polymerase chain reaction using specific primers. Results. A significant difference was found between the patients with FMF-related amyloidosis and the control group as for genotype distribution of ACE I / D variant (P < .05). The ACE D/D and I / D genotypes were more frequent in the patients with FMF-related amyloidosis while the I/I genotype was less frequent in the same patients. The FMF patients (with and without amyloidosis) had significantly higher percentages of the D/D and I/D genotypes than the healthy controls (P < .05). Comparison between the subgroups of FMF patients, divided into those with and without amyloidosis, yielded a significant correlation according to ID+II versus DD genotypes (P < .03, odds ratio, 3.24; 95% confidence interval, 1.05 to 12.01). Conclusions. Based on these observations, the ACE I/D variant D/D genotypes implicate a possible risk in the FMF-related amyloidosis among Turkish population

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease