Gene Polymorphisms in FMF and Their Association With Amyloidosis α Tumor Necrosis Factor (original) (raw)
Related papers
Tumor Necrosis Factor- Gene Polymorphisms in FMF and Their Association With Amyloidosis
Clinical and Applied Thrombosis/Hemostasis, 2012
Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by periodic provocative attacks of fever with peritonitis, pleuritis, arthritis, or eriseplemya. Tumor necrosis factor-a (TNF-a) plays an important role in the regulation of the immune response as a part of the cytokine network, including activation of macrophages and apoptosis. We investigated the possible association of TNF-a promoter À1031T/C and À308G/A polymorphisms in 86 FMF patients carrying M694 V homozygous mutation and 100 matched healthy controls both from Iranian Azeri Turks. Our data showed that patients with TNF-a À308 GG are more susceptible to the development of amyloidosis and arthritis (P value <.05). These data also showed that the frequency of TNF-a À308 A allele is considerably low among patients with amyloidosis, and it may have protective role among them (odds ratio [OR] ¼ 0.083, w 2 ¼ 5.46, P value ¼ .003). Further evaluation of this polymorphism may be important and need further studies.
The role of TNF-α and PAI-1 gene polymorphisms in familial Mediterranean fever
Modern Rheumatology, 2013
Objectives Familial Mediterranean fever (FMF) is one of the most serious inherited inflammatory disorders among Jewish, Armenian, Turkish and Arab populations. The imbalance between pro-and anti-inflammatory cytokines may play a role in its etiology. We have investigated whether tumor necrosis factor-alpha (TNF-a) and plasminogen activator inhibitor 1 (PAI-1) gene polymorphisms are associated with FMF and evaluated the relationship between these polymorphisms and genotypic manifestation of FMF. Methods We investigated single nucleotide polymorphisms of the TNF-a promoter at positions -308 G/A and the PAI-1 4G/5G gene polymorphism in peripheral blood leukocytes collected from 177 individuals with FMF with different genotype combinations. All of the polymorphisms of TNF-a and PAI-1 were detected by PCR and restriction fragment length polymorphism analysis. Results There were no association between the TNF-a/ 308 genotypes and mutations in FMF. In contrast, the PAI-1 4G/5G gene polymorphism may have a significant effect in FMF disease. Conclusions Screening with PAI-1 gene polymorphism tests may be beneficial for tracing future FMF patients. However, further investigations are needed to reach a conclusion on the association between PAI-1 polymorphisms and FMF.
The Turkish journal of pediatrics
The aim of this study was to examine whether polymorphisms at serum amyloid A (SAA) and tumor necrosis factor-alpha (TNF-alpha) genes are associated with development of amyloidosis in familial Mediterranean fever (FMF) patients. Seventy-three FMF patients with amyloidosis and 100 other FMF patients without amyloidosis of known genotypes and 100 healthy control subjects were analyzed. There was a significant difference in the frequency of alpha/alpha genotype at the SAA1 locus between FMF patients with amyloidosis and controls and FMF patients without amyloidosis. The frequencies of the alpha/alpha genotype and alpha alleles at SAA1 locus were significantly higher in the FMF patients with amyloidosis. The frequencies of the alpha allele at SAA1 locus in FMF patients with amyloidosis, without amyloidosis and controls were 85.6%, 49.5% and 42.5%, respectively. We demonstrated that alpha/alpha genotype at SAA1 gene might have modifying effects on the development of amyloidosis. Determin...
Pediatrics, 2000
Objective. The gene causing familial Mediterranean fever (FMF)-an autosomal recessive disease characterized by recurrent short episodes of fever associated most commonly with peritonitis, pleuritis, and arthritis-has recently been found and several mutations identified. The most severe complication of the disease is amyloidosis, which can lead to renal failure. The aim of this study was to investigate the role of genetic versus nongenetic factors on the phenotype as well as on the development of amyloidosis in FMF in a large and heterogeneous group of patients. Methodology. We studied 382 patients from 4 ethnic origins living in different environments: North African Jews, other Jews, Turks, Armenians living in the United States, and Armenians from Yerevan, Armenia. Information regarding amyloidosis was available for 371 patients. We examined the association between the mutation M694V and the development of amyloidosis, and we also compared the clinical characteristics of the inflammatory attacks in patients from different ethnic origins, while controlling for the type of mutation. Results. A significant association was found between amyloidosis and the most common mutation in exon 10 of the FMF gene (MEFV), M694V (for M694V homozygotes, relative risk ؍ 1.77; 95% CI ؍ 1.16-2.71). Amyloidosis was present in 44 of 171 homozygous FMF patients (25.7%), in 22 of 143 compound heterozygous FMF patients (15.4%), and in 7 of 57 patients carrying other mutations (12.3%). In homozygotes for M694V who had not been treated with colchicine before 20 years of age, the risk of amyloidosis developing before this age was 61.0%. In our series, there were no cases of amyloidosis in 16 patients carrying the common mutation E148Q. We found that the type and severity of the FMF inflammatory symptoms were associated with both the genotype and the country of residence of the patient. Conclusions. In the light of the high frequency of amyloidosis in homozygotes for the mutation M694V, colchicine treatment should be given to this group irrespective of the severity of the inflammatory attacks to prevent the development of amyloidosis. Our findings also suggest that factors other than genotype, such as environment or genes other than MEFV, play a role in the determination of the severity of the inflammatory attacks in FMF. Pediatrics 2000;105(5).
Rheumatology International, 2007
The most important complication of FMF is the development of amyloidosis. It is more common in the eastern Mediterranean compared to the US. The individual response to endotoxin may have a signiWcant eVect on the development of amyloidosis in FMF patients. To investigate the association between CD14 promotor C-159T polymorphism and development of amyloidosis, one hundred and forty-six patients who had FMF and had not developed amyloidosis; 26 with FMF and secondary amyloidosis and 92 controls were genotyped at the CD14-C159T locus. There was no diVerence between the genotype distribution of FMF patients (CC 30.0%, CT 50.0%, TT 20.0%) and controls (CC 29.2%, CT 45.8%, TT 25%); or between FMF patients with amyloidosis (CC 30.8%, CT 53.8%, TT 15.4%) or without amyloidosis (CC 29.2%, CT 45.8%, TT 25%). Our study shows that the CD14-C159T polymorphism is not associated with FMF or development of amyloidosis in the population studied. The eVect of the genetic variations in the endotoxin signaling pathway under diVerent environmental conditions such as high and low endotoxin exposure remain to be determined.
The role of the R92Q TNFRSF1A mutation in patients with familial mediterranean fever
Arthritis Care Research, 2010
Objective. To define the frequency of the R92Q tumor necrosis factor receptor-associated periodic syndrome (TRAPS) mutation in patients with familial Mediterranean fever (FMF) and to study the role of this mutation in FMF. Methods. Ninety-two FMF patients and 250 controls were genotyped for the R92Q mutation. The frequency of R92Q was assessed among 5 groups of FMF patients. Results. R92Q was found in 6% of the controls, with an especially high carrier rate among Moroccan Jews (8%). R92Q was found in 3 (3.2%) of the 92 FMF patients, 1 homozygous for the MEFV M694V mutation and 2 heterozygous for M694V. All 3 patients showed partial response to colchicine. R92Q was not found in patients unresponsive to colchicine, nor was it found in patients with amyloidosis or in patients with FMF-like disease without MEFV mutations. Conclusion. The frequency of the R92Q mutation in FMF patients is comparable with that of controls. Despite the fact that TRAPS and FMF share common biochemical pathways, we found no evidence for an interaction between these two genes.
Role of the R92Q TNFRSF1A mutation in patients with familial Mediterranean Fever
Arthritis Care & Research, 2010
Objective. To define the frequency of the R92Q tumor necrosis factor receptor-associated periodic syndrome (TRAPS) mutation in patients with familial Mediterranean fever (FMF) and to study the role of this mutation in FMF. Methods. Ninety-two FMF patients and 250 controls were genotyped for the R92Q mutation. The frequency of R92Q was assessed among 5 groups of FMF patients. Results. R92Q was found in 6% of the controls, with an especially high carrier rate among Moroccan Jews (8%). R92Q was found in 3 (3.2%) of the 92 FMF patients, 1 homozygous for the MEFV M694V mutation and 2 heterozygous for M694V. All 3 patients showed partial response to colchicine. R92Q was not found in patients unresponsive to colchicine, nor was it found in patients with amyloidosis or in patients with FMF-like disease without MEFV mutations. Conclusion. The frequency of the R92Q mutation in FMF patients is comparable with that of controls. Despite the fact that TRAPS and FMF share common biochemical pathways, we found no evidence for an interaction between these two genes.
Serum Amyloid A Type 1 Gene Polymorphism in Egyptian Children with Familial Mediterranean Fever
Pathobiology, 2016
Background: Since spontaneous inflammation is an important contributor to familial Mediterranean fever (FMF), genetic variants mediating inflammation are of interest. We investigated gene variants in the acute-phase serum amyloid A type 1 (SAA1), a sensitive marker of inflammatory activity, and their association with susceptibility and severity of FMF. Methods: The genotypes of 2 single-nucleotide polymorphisms within exon 3 of SAA1 (2995C/T and 3010C/T) were determined in 105 Egyptian children with FMF and in 125 controls by polymerase chain reaction-restriction fragment length polymorphism. Genotyping of the causative MEFV mutations was performed by reverse hybridization. Results: The M694I mutation was the most frequent allele (42.8%), followed by V726A (18.6%), M680I (17.1%), E148Q (11.9%) and M694V (9.0%). The frequency of the SAA1 α, β and γ alleles was not significantly different between FMF patients and controls. The genotype frequency of SAA1 α/α was higher in patients than...
Interleukin-1Ra rs2234663 and Interleukin-4 rs79071878 Polymorphisms in Familial Mediterranean Fever
Gene, 2016
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 N 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 N 0.05, OR: 1.131, CI 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.
Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF)
European Journal of Human Genetics, 1998
FMF patients with 0, 1 or 2 MED mutations. We showed that homozygosity for this mutation was significantly associated with a more severe form of the disease. In homozygous patients, the disease started earlier (mean age 6.4 + /-5 vs 13.6 + /-8.9) and both arthritis and pleuritis were twice as frequent as in patients with one or no M694V mutation. Moreover, 3/3 patients with amyloidosis displayed two MED mutations. No association was found with fever, peritonitis, response to colchicine and erysipeloid eruption. The present result strongly suggests the potential prognostic value of the presence of this mutation.