Serum amyloid A1 -13 T/C alleles in Turkish familial Mediterranean fever patients with and without amyloidosis

Previously reported studies concerning the effect of homozygosity of the 1.1 allele of the SAA gene found a correlation between this haplotype and susceptibility to amyloidosis in FMF patients. Another report revealed a strong association between SAA1 -13T/C and secondary amyloidosis in the rheumatoid arthritis patient group. In this study, we aimed to determine the effect of SAA1 -13T/C in FMF patients with and without amyloidosis. The study cohort, consisting of 166 patients with FMF was divided into two groups, according to the presence (n=66) or absence (n=100) of renal amyloidosis at study entry. MEFV gene mutation analysis and allelic variant of SAA1 gene -13 T/C was analyzed according to the previously described techniques. SAA1 -13 T allele frequencies were 0.5816, 0.23 and 0.4242 in controls, FMF patients and FMF-amyloidosis patients respectively. The difference between controls vs. FMF patients and FMF-amyloidosis patients were 0.0002 and 0.1673 respectively. It was 0.0071 for FMF-patients vs. FMF-amyloidosis. When 694 M/V homozygous nonamyloid-FMF group was compared with 694 M/V carriers of the FMF-amyloidosis group, the difference was 0.049. When carrying TT allele was considered, the difference between controls vs. FMF patients and FMF-amyloidosis patients were 0.0001 and 0.58. It was 0.0003 for FMF patients vs. FMF-amyloidosis. When 694 M/V homozygous nonamyloid-FMF group was compared with 694 M/V carriers of the FMF-amyloidosis group, the difference was 0.03. Carrying SAA -13T in homozygote state revealed a 7.9 (95% CI 3.6 -17.5) fold risk for the occurrence of amyloidosis when compared with FMF patients without amyloidosis. This was 8.75 (95% CI 3.0 - 25.1) when 694 M/V homozygotes were taken into consideration. Our data revealed that the genotype SAA1 -13T has at least an effect on the development of amyloidosis. As more data on this polymorphism accumulate, we will understand its effect on the pathogenesis of amyloidosis in FMF.     

Mutational spectrum in the MEFV and TNFRSF1A genes in patients suffering from AA amyloidosis and recurrent inflammatory attacks.

BACKGROUND: Among hereditary fevers characterized by recurrent attacks of fever and organ localized inflammation, familial Mediterranean fever (FMF), and tumour necrosis factor receptor superfamily 1A (TNFRSF1A) receptor associated periodic syndrome (TRAPS) are diseases with identified genes that can be associated with renal amyloidosis of the AA type. In this study we have characterized FMF and TRAPS genotypes in 38 unrelated patients suffering from amyloidosis AA and recurrent inflammatory attacks. METHODS: Mutations of the MEFV and TNFRSF1A genes, responsible respectively for FMF and TRAPS, were searched for by amplifying, using polymerase chain reaction (PCR), genomic DNA, and direct sequencing. RESULTS: Twenty-seven patients (71%) carried mutations in MEFV (22 patients with two mutations, two patients with a single mutation) or TNFRSF1A genes (three patients). Patients with MEFV mutations belonged to the classical at-risk ethnic group for FMF: Sephardic Jews, Turks, Armenians, and Arabs from the Maghreb. The main genotype encountered was M694V/M694V (19/22), one Turkish patient was M680I/M680I, and two Arab patients from the Maghreb were M694I/M694I. We found three Caucasian patients with the C55S, C70Y, R92Q mutations in the TNFRSF1A gene. CONCLUSIONS: In this series we observed that FMF is the main cause of AA amyloidosis in Sephardic Jews and Turks. MEFV and TNFRSF1A mutations were found in only 6 of 14 Arab patients from the Maghreb. We found three families (one Caucasian and two from Maghreb) with AA amyloidosis without MEFV or TNFRSF1A mutations, suggesting that other genetic cause(s) exist(s). The characterization of mutations in MEFV and TNFRSF1A is important for the therapeutic behaviour of AA amyloidosis associated with inherited recurrent fever.     

Familial Mediterranean fever (FMF) and renal AA amyloidosis--phenotype-genotype correlation,treatment and prognosis

Familial Mediterranean fever (FMF) is an autosomal recessive disease, which primarily affects the population surrounding the Mediterranean basin. It is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis or erysipelas-like erythema. Amyloidosis, causing renal failure, is one of the most severe complications of the disease. The gene associated with FMF (MEFV) has been recently isolated. Phenotype-genotype correlation studies revealed that amyloidosis was more common in FMF patients originating from North-Africa who were homozygous for the M694V mutation. Such a correlation was not found in Turkish patients. The risk of amyloidosis is increased in male FMF patients and in patients bearing polymorphism a/a in the SAA1 gene. Colchicine is the chosen drug for the treatment of FMF and can prevent amyloidosis.     

Two sisters with familial Mediterranean fever: lack of correlation between genotype and phenotype?

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and serositis. The most important complication of FMF is renal amyloidosis, which determines the prognosis. The gene coding the disease (MEFV) is identified on the 16th chromosome. The most common MEFV mutations are M694V, M680I, V726A and M694I located on exon 10 and E148Q located on exon 2. Unfortunately, genotype-phenotype correlation is not well established and there are unexplained ethnic differences in amyloidosis rates. We report two sisters with a common genotype (M694V/M694V) presenting with different phenotypic characteristics: one complaining of intermittent abdominal pain, arthritis and fever, while the other was suffering from intermittent pleuritis and fever during attacks. The observation of different phenotypic presentations with a common genotype in two family members shows that different phenotypes cannot be explained by particular mutations. To understand the correlation between genotypic and phenotypic FMF variants the existence of complex alleles, modifier loci, genetic heterogeneity and possible epigenetic factors should be studied extensively.     

Long-term outcome of renal transplantation in patients with familial Mediterranean fever amyloidosis: a single-center experience

Although recurrence of amyloid A deposition in the allograft can be seen in patients with secondary amyloidosis due to familial Mediterranean fever (FMF), renal transplantation remains to be a choice of treatment for end-stage renal disease. The aim of this study was to determine short- and long-term results of renal transplantation in patients with FMF amyloidosis. We compared the outcomes of 17 patients with FMF amyloidosis among 431 (3.9%) transplants with 209 control patients. We observed 93% and 94% graft and patient survivals at 1 year, and 89% and 90% at 5 years. Also, the mean serum creatinine levels at 1 and 5 years posttransplant were similar. Recurrence of amyloidosis was documented in two allograft recipients presenting with nephrotic range proteinuria (12%), one of whom lost the allograft due to recurrence. Eleven patients had FMF gene analysis. The results of MEFV mutation analyses were: M694V/M694V homozygote in six patients, M694V/EQ148 in one patient, M694V/V726A in one patient, 680M-I/E148Q in one patient. FMF gene analysis was negative in two patients. Recurrence was noticed in one patient with M694V/M694V, while the other did not have an FMF gene analysis. Colchicine was reduced in nine patients due to side effects. In conclusion, the long-term outcomes of transplantation in patients with amyloidosis secondary to FMF is similar to that in the general transplant population and maintenance colchicine, even at low dose, appears to effectively prevent recurrence of amyloidosis in the allograft.     

The relationship between the MEFV genotype, clinical features, and cytokine-inflammatory activities in patients with familial mediterranean fever

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by periodic attacks of fever and polyserositis. The effects of the MEFV genotype differences on clinical picture and inflammatory activity have not been well documented. The aim of this study was to investigate levels of conventional inflammation markers, procalcitonin, interleukin levels, TNF-alpha, and C5a levels in patients with FMF who had different MEFV genotypes and compare them with those of healthy subjects. The study consisted of 41 patients with FMF (F/M: 23/18), and 31 healthy subjects (F/M: 18/13). Tests were performed during the attack-free period. White-blood cell count, CRP and IL-8 levels were higher in patients with FMF than in healthy subjects (p < 0.05) and also higher in M680I carriers than in the patients with M694V allele carriers. However, ESR, fibrinogen, procalcitonin, IL-6, C5a, TNF-alpha, and IgD levels were not significantly different between patients and healthy subjects (p > 0.05). Arthralgia or arthritis was significantly higher in M694V carriers than in non-M694V carriers (p < 0.05). It is concluded that the clinical features and inflammatory-cytokine activities were higher in patients with FMF during the attack-free period than in healthy subjects, and the different genotype might be related to different clinical pictures.     

SAA1 alpha/alpha alleles in amyloidosis

BACKGROUND: Amyloidosis, mainly AA type, is one of the common diseases in nephrology clinics in Turkey. AA type amyloidosis is a complication of various chronic infections or inflammatory diseases such as familial Mediterranean fever (FMF), rheumatoid arthritis (RA), tuberculosis and bronchiectasis. A controversy exists in the literature regarding the relationship between SAA1 genotypes and AA type amyloidosis. This study aimed to investigate SAA1 gene polymorphism in different patient groups: 1) amyloidosis, 2) FMF and 3) healthy controls. METHODS: Eighty-two patients from the three groups were included in the study: 1) amyloidosis, 2) FMF without amyloidosis, and 3) healthy controls. SAA1 genotypes were studied by the polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The homozygous alpha/alpha genotype is the most common SAA1 genotype among patient groups with amyloidosis, and the alpha/alpha genotype frequency is significantly higher than in healthy controls (68 vs. 38%, p<0.05). CONCLUSIONS: The SAA1 alpha/alpha genotype is a risk factor for AA type amyloidosis in Caucasoid populations and more studies are needed to investigate why the gamma/gamma genotype is associated with AA type amyloidosis in Japan.     

The Relationship between the MEFV Genotype,Clinical Features,and Cytokine-Inflammatory Activities in Patients with Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by periodic attacks of fever and polyserositis. The effects of the MEFV genotype differences on clinical picture and inflammatory activity have not been well documented. The aim of this study was to investigate levels of conventional inflammation markers, procalcitonin, interleukin levels, TNF-alpha, and C5a levels in patients with FMF who had different MEFV genotypes and compare them with those of healthy subjects. The study consisted of 41 patients with FMF (F/M: 23/18), and 31 healthy subjects (F/M: 18/13). Tests were performed during the attack-free period.

White-blood cell count, CRP and IL-8 levels were higher in patients with FMF than in healthy subjects (p < 0.05) and also higher in M680I carriers than in the patients with M694V allele carriers. However, ESR, fibrinogen, procalcitonin, IL-6, C5a, TNF-alpha, and IgD levels were not significantly different between patients and healthy subjects (p > 0.05). Arthralgia or arthritis was significantly higher in M694V carriers than in non-M694V carriers (p < 0.05). It is concluded that the clinical features and inflammatory-cytokine activities were higher in patients with FMF during the attack-free period than in healthy subjects, and the different genotype might be related to different clinical pictures.     

Long-Term Outcome of Renal Transplantation in Patients With Familial Mediterranean Fever Amyloidosis: A Single-Center Experience

IntroductionFamilial Mediterranean fever (FMF) is an autosomal-recessive disorder, affecting multiple organs. The AA type of amyloidosis is most common and serious complication cause nephropathy and end-stage renal disease (ESRD). Renal transplantation (RTX) remains treatment of choice for ESRD. We aimed to investigate long-term results of RTX in patients with FMF amyloidosis.Patients and MethodsWe compared the outcomes of 18 patients (12 men and 6 women) with FMF amyloidosis among 601 (2.9%) transplants with 200 control patients. Demographic data and gene analysis were evaluated.ResultsIn our study the 1-year graft and patient survivals were 94.44% and 100%, respectively. At 5 years after RTX, they were 94.73% and 88.88%, respectively, in the FMF group without difference from controls. Mean creatinine level at 1 and 5 years were 1.43 ± 0.54 and 1.73 ± 0.89, respectively. The results of MEFV mutation analyses were: M694V/M694V homozygote in 1 patient, M694V/EQ148 in 3, M694V/V726A in 2, 680M-I/E148Q in 3, M694V/M680I in 5, R202Q/M680I in 2, and M694V/R202Q in 2. Recurrence was noticed in 1 patient with M694V/M680I. One patient died because of graft loss and cardiac complications with M694V/M680I gene analysis. Colchicine was reduced in 4 patients owing to side effects.ConclusionLong-term outcomes of transplantation in patients with amyloidosis secondary to FMF is similar to that in the general transplant population and maintenance colchicine, even after decreasing its dose, effectively prevents recurrence of amyloidosis in the allograft.     

MEFV gene mutations in familial Mediterranean fever phenotype II patients with renal amyloidosis in childhood: a retrospective clinicopathological and molecular study.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring attacks of fever and serositis. The definition of the mutated gene has allowed molecular diagnosis of the disease. The most important complication of FMF is the development of AA type secondary amyloidosis. In a group of patients clinically designated as phenotype II amyloidosis patients, renal amyloidosis develops without being preceded by typical attacks of the disease. In this study, the mutations of the MEFV gene were analysed in a group of patients clinically recognized as phenotype II. METHODS: DNA samples were obtained from tissue samples of the subjects. PCR-RFLP methods were used to analyse the M694V, M680I, V726A and E148Q mutations that have been previously defined by us to be the most common mutations in our Turkish cohort. RESULTS: The distribution of the four most common mutations among phenotype II patients was 38% for M694V, 8% for M680I, 4% for V726A and 4% for E148Q. CONCLUSIONS: In phenotype II amyloidosis patients, the distribution of the four common MEFV mutations was not significantly different from that found in all FMF patients with typical symptoms who do or do not develop amyloidosis. We therefore suggest that secondary genetic or environmental factors are operative in the development of secondary amyloidosis in patients with FMF.     

Phenotype 2 Familial Mediterranean Fever: Evaluation of 22 Case Series and Review of the Literature on Phenotype 2 FMF

Familial Mediterranean fever (FMF) is an autosomal recessive autoimmune disorder characterized by recurrent bouts of fever and serosal inflammation. FMF may be complicated by AA-type amyloidosis, worsening the prognosis, with associated renal failure in some patients. Complication rate varies with race, being as high as 60% in Turks and as low as 2% in Armenians. In a few cases of patients with FMF (phenotype 2), amyloid nephropathy may be the presenting manifestation. This study included 420 patients who were admitted to the Nephrology and Rheumatology Departments of Atatürk Education and Research Hospital with unexplained proteinuria/nephrotic syndrome. The initial screening test for amyloidosis was the presence of significant proteinuria (300 mg/24 h). All MEFV gene exons were screened for causative mutations by direct DNA sequencing to check for any mutations. There were 22 phenotype 2 FMF patients with 27 allelic variants. The most prevalent allelic variants were M694V (10/27, 37%) and E148Q (7/27, 26%). Phenotype 2 FMF is not as rare as it was thought before; this should be kept in mind for all patients with unexplained proteinuria and/or acute phase response in high-risk ethnic groups for FMF.     

Higher thrombin activatable fibrinolysis inhibitor levels are associated with inflammation in attack-free familial Mediterranean fever patients

Background: Coagulation abnormalities have been reported in familial Mediterranean fever (FMF) patients with amyloidosis and nephrotic syndrome; but there is not enough data about the continuity of the thrombogenic activity in FMF patients in clinical remission. The purpose of this study was to assess thrombin activatable fibrinolysis inhibitor (TAFI) levels and its relationship with fibrinolytic activity and also evaluate relationships between mutations and clinical signs in attack-free patients without amyloidosis. Methods: Seventy-nine FMF patients and 40 healthy adults were included. The study group was divided into five groups as follows: first group, homozygote M694V; second group, homozygote M680I; third group, M694V in one allele, the other allele have other mutations or not; fourth group, other mutations; and fifth group, no mutation. Results: Serum TAFI levels were significantly increased in patients compared with healthy individuals (116.64?±?21.8 vs. 78.48?±?19.7?μg/mL, p?r?=?0.247, p?=?0.029 and r?=?0.252, p?=?0.032, respectively). Mean fibrinogen and TAFI levels were significantly higher in Group 1 than the other groups (p?=?0.04 and p?=?0.001, respectively) and in Group 3 it was higher than Groups 2, 4 and 5 (p?=?0.04 and p?=?0.001, respectively). Conclusions: High level of TAFI antigen in attack-free period of FMF disease shows ongoing subclinical inflammation and hypercoagulability. Clinicians should be careful about thrombosis even in patients at clinical remission. Also, genetic tests must be considered to predict clinical outcome and to reduce complications of FMF disease.     

Familial Mediterranean fever

Familial Mediterranean fever (FMF) is the most frequent periodic syndrome characterized by recurrent attacks of polyserositis. Fever, abdominal pain, chest pain, and arthritis/arthralgia are the leading symptoms. It is an autosomal recessive disorder, which primarily affects Jewish, Armenian, Turkish, and Arab populations. The FMF gene (MEFV) has recently been cloned to chromosome 16p, which encodes pyrin. Genotype-phenotype correlation is not well established. Amyloidosis is the most severe complication of FMF. The SAA1-/ genotype was associated with an increased risk of amyloidosis. Colchicine treatment not only decreases the frequency and severity of attacks, but also prevents amyloidosis. Certain vasculitides, namely Henoch-Schonlein purpura and polyarteritis nodosa, are more frequent among FMF patients.     

Successful treatment of renal AA amyloidosis in familial Mediterranean fever with pegylated alpha-2a interferon

Renal AA amyloidosis is a severe consequence of chronic inflammatory diseases such as familial Mediterranean fever (FMF). FMF is caused by mutations in the MEFV gene, resulting in defective control of granulocyte-mediated inflammation. Interferon-alpha is known to induce MEFV expression in monocytes and granulocytes in vitro. We present the first case of colchicine-resistant FMF in which a durable disease remission and regression of renal amyloidosis was induced by chronic treatment with pegylated interferon-alpha.     

150例不同基因型慢性乙型肝炎患者逆转录聚合酶区耐药变异位点特征及耐药影响因素

目的观察150例不同基因型慢性乙型肝炎（CHB）患者乙型肝炎病毒（HBV）DNA逆转录聚合酶（RT）区域耐药变异位点特征,并分析耐药影响因素。 方法回顾性分析唐山市传染病医院2018年1月至2020年12月收治的行RT区检测的150例CHB患者的临床资料,比较不同基因型CHB患者RT区耐药变异位点特征,根据HBV DNA RT区测序结果将患者分为耐药变异位点突变组（突变组）与未发生耐药变异位点突变组（未突变组）,采用Logistic回归分析耐药变异位点突变的影响因素。 结果150例CHB患者中74例发生耐药变异位点突变,76例未发生耐药变异位点突变;耐药变异位点突变发生在B和C基因型中,其中B基因型3例,C基因型71例;以rtM204I/V/S、rtL180M + rtS202G/I + rtM204I/V/S、rtL180M + rtM204I/V/S、rtA181T/V占比最高;B基因型CHB患者仅有rtM204I/V/S、rtL180M + rtS202G/I + rtM204I/V/S、rtL180M + rtM204I/V/S突变,C基因型患者RT区耐药变异位点较多;耐药变异位点突变组患者抗病毒治疗状况为持续治疗（χ² = 57.075、P < 0.001）、不适当停药（χ² = 5.543、P = 0.019）、基因分型C基因型（χ² = 3.062、P = 0.003）占比高于未发生耐药变异位点突变组,HBV DNA（t = 14.579、P < 0.001）、HBsAg（t = 21.863、P < 0.001）高于未突变组,差异均有统计学意义。两组患者年龄、性别、HBeAg、饮酒史、家族CHB史、高血压史、糖尿病史、高血脂史、是否同期接受其他治疗、肝纤维化、病程、总胆红素（TBil）、白蛋白（ALB）、天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、谷氨酰转肽酶（GGT）和碱性磷酸酶（ALP）差异均无统计学意义（P均> 0.05）。单因素Logistic回归分析显示,抗病毒治疗（OR = 5.765、P < 0.001）、不适当停药（OR = 2.757、P = 0.021）、HBV DNA（OR = 1.617、P = 0.004）、HBsAg（OR = 2 296.820、P < 0.001）以及基因分型（OR = 12.307、P < 0.001）均为CHB患者耐药发生的危险因素;经多因素Logistic回归分析显示,抗病毒治疗（OR = 11.141、P = 0.006）、不适当停药（OR = 5.962、P = 0.019）、HBV DNA（OR = 1.849、P = 0.040）、HBsAg（OR = 5 490.477、P < 0.001）以及基因分型（OR = 12.456、P < 0.001）为CHB患者耐药发生的危险因素,差异均有统计学意义。 结论入组不同基因型CHB患者HBV DNA RT区耐药变异位点存在差异,C基因型患者占比较高,耐药变异位点多;患者耐药受不适当停药、HBV DNA及HBsAg水平影响,临床可针对各项危险因素制定干预措施,并在治疗期间为患者更换抗病毒药物,以减少病毒突变株的产生。     

Autosomal-dominant periodic fever with AA amyloidosis: Novel mutation in tumor necrosis factor receptor 1 gene Rapid Communication

BACKGROUND: The recent identification of genes responsible for syndromes of periodic fever with amyloidosis has opened the way to a molecular diagnosis of hereditary AA amyloidosis. METHODS: A Belgian woman presented for genetic counseling. Three first-degree relatives had a diagnosis of renal amyloidosis with a history of recurrent fever and inflammatory episodes. Medical records and pathological specimens were obtained from all physicians who had been in charge of her three relatives. Immunohistochemical staining was performed on paraffin-embedded material. A mutation search was performed in the MEFV (Mediterranean fever) and tumor necrosis factor receptor 1 (TNFR1 or TNFRSF1A) genes causing familial Mediterranean fever (FMF) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), respectively. RESULTS: The family history was consistent with autosomal-dominant transmission of periodic fever with arthralgias, abdominal pain, and eventual AA amyloidosis involving the kidneys, digestive tract, and thyroid. Recurrent amyloidosis in kidney graft was demonstrated in one patient and was suspected in the other. A novel heterozygous mutation (C55S) in TNFRSF1A was identified in the affected patient available for genetic testing but not in the asymptomatic woman requiring counseling. No mutation was detected in MEFV. CONCLUSIONS: We report a novel mutation (C55S) in TNFRSF1A, resulting in autosomal-dominant periodic fever and AA amyloidosis. This condition, known as TRAPS, should be added to the differential diagnosis of hereditary renal amyloidosis, with obvious implications for management and genetic counseling.     

A case of familial Mediterranean fever with amyloidosis as the first manifestation

We describe a 22-year-old Turkish woman with nephrotic syndrome who had a history of acute myelocytic leukemia. After careful clinical evaluation, the patient underwent a renal biopsy. Light microscopic examination showed deposition of Congo-positive material both in the mesangium and around the small vessels. By histochemical analyses, the deposited material was proved to be amyloid A (AA). Because the patient's history did not reveal any event that might explain the development of secondary amyloidosis, she was screened for mutations causing familial Mediterranean fever (FMF) and was found to be homozygous for the M694V mutation by denaturing gradient gel electrophoresis. We recommend that FMF-Phenotype II and the development of amyloid nephropathy, before or without other symptoms of FMF, should be kept in mind in the face of unexplained proteinuria/amyloidosis, especially in high-risk ethnic groups. © 2001 by the National Kidney Foundation, Inc.     

Association between ABCB1 (MDR1) gene 3435 C>T polymorphism and colchicine unresponsiveness of FMF patients

The multidrug resistance gene-1 (MDR1, adenosine triphosphate-binding cassette transporter: ABCB1, P-glycoprotein) encodes membrane proteins that play a crucial role in protecting cells from xenobiotics, chemicals, and drugs. The TT genotype of 3435 codon in exon 26 of MDR1 gene causes overexpression of gene activity and effluxes many chemically diverse compounds across the plasma membrane. We studied the association between C3435T polymorphisms (single nucleotide polymorphism) of MDR1 gene and colchicine-resistant familial Mediterranean fever (FMF) patients. Total genomic DNA samples from 52 FMF patients of colchicine unresponsiveness were used for FMF (MEFV) and MDR1 genes profile analyses. Target genes were genotyped by multiplex PCR-based reverse-hybridization Strip Assay method. The preliminary current results showed increased T allele frequency (0.596) in colchicine unresponsiveness of FMF patients. The distributions of the CC, CT, and TT genotypes in colchicine nonresponder FMF patients were 17%, 46%, and 37%, respectively. Our results indicate that C3435T polymorphism in exon 26 of MDR1 gene is associated with colchicine resistance in nonresponder FMF patients during the common therapy protocol.     

Multiple visceral hematomas in a child with familial Mediterranean fever: polyarteritis nodosa

A 14-year-old girl was diagnosed with familial Mediterranean fever (FMF) with homozygous for M694V mutation of the MEFV gene and was started on colchicine therapy 4 years before admission to our hospital. She was uncompliant to therapy and was admitted to a local hospital with complaining of fever, malaise, abdominal pain and artralgia lasting for 2 months. Multiple hypoechogenic mass lesions were detected on liver and kidneys with ultrasonography (US) and diagnosed to be hematomas by laparoscopic examination. She was referred to our hospital because of development of convulsions. On physical examination her blood pressure was 140/90 mmHg and body temperature was 39 degrees C. She was pale and extremely cachectic, with atrophic muscles of the extremities. She had diffuse abdominal tenderness and hepatosplenomegaly. Laboratory investigations revealed a hemoglobin of 9.8 g/dl, white blood cell count 9,900/mm3, platelets 213,000/mm3, erythrocyte sedimentation rate (ESR) 112 mm/h, C- reactive protein (CRP) 78 mg/L (normal < 2 mg/L) and fibrinogen 500 mg/dl. Electrolytes, renal and hepatic functions and urinalysis were normal. Examinations of peripheric blood smear and bone marrow aspiration were normal. X-rays of bones and chest showed no pathological finding. Protrombine, partial thromboplastine and bleeding times were normal. Bacterial cultures of blood, urine and stool grew no organisms. Serological tests for hepatitis B and C, cytomegalovirus, salmonella and brucella were negative.     

Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis

Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease.