Homozigot E148q Varyantına Sahip Ailevi Akdeniz Ateşi Vakalarında ve Sağlıklı Toplumda DNA MEFV (Mediterranean Fever) Gen Analizi ve E148q Allel Sıklığının Taranması

Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and serositis, common in populations of Turkish, Armenian, Arab and Sephardic Jewish origin. The disease is associated with a number of mutations of the MEFV gene, which codes for a protein named “pyrin”. To date 246 variants responsible for the disease were identified in the MEFV gene, one such a variant is E148Q in exon 2 of the gene. The role of E148Q pyrin gene variant in the development of FMF remains inconclusive. Some authors believe it causes the disease, whereas others favor the concept of a noncausative role. The aim of this study performing MEFV gene sequence analysis in order to detect an associated novel mutation/variant; determining the frequency of E148Q allele in healthy society, and ultimately, clarifying the controversy about whether defected E148Q allele causes polymorphism or a mutation resulting in illness. After informed consents were obtained from patients with previously detected homozygous E148Q allele with strip assay and the FMF clinical forms were filled in for those, DNA sequence analysis was performed from peripheral blood samples in order to determine whether there are associated novel or known mutations in other MEFV gene exons or not. E148Q allele frequencies of the parents and that of control group consisting of 100 healthy individuals were determined. 44% (n:8) of the patients were males and 56% (n:10) of the patients were females. Age at the onset of disease was 5±3.7 (median 5) years, age at diagnosis was 8.1±3.4 (median 7) years, and the period between onset and diagnosis was 2.7±2.7 (median 1.5) years. Age at onset was ≤ 5 years at 64.3% (n:9) of the patients, diagnosis age was >6 years at 61.1% (n:11) of patients. Presenting manifestations were abdominal pain (78.5%), fever (71.4%), arthralgia (57.1%), pleuritis (28.5%) and myalgia (7.1%). With colchicine treatment, vii significant decrement in annual number of attacks, duration of attacks and disease activation scores were observed (p<0.05). Full remission in 78.5% (n:11) of patients and partial remission in 21.5% (n:3) were achieved, there were no patients unresponsive to treatment. There were no difference in terms of achievement of full or partial remission, possessing low or moderate disease activation score, living without attack or with >20 attacks/year between groups carrying associated variants (detected as R314R, P369S, R408Q, E474E, Q476Q, D510D, P588P) and those with no associated variants. In control group consisting of 100 healthy individuals, the frequency of E148Q allele was found to be 6.5%. The high frequency of E148Q allele in healthy population and asymptomatic clinic of E148Q homozygous parents do not falsify the hypothesis that E148Q variant is related with disease, considered the symptomatic clinic of 78% of patients homozygous for E148Q, presence of response to colchicine treatment and detection of no associated variant in DNA sequence analysis at those patients.