Ailevi akdeniz ateşi hastalarında MEFV geninin tam DNA sekans analizi ve klinik bulgular ile ilişkisi
Küçük Resim Yok
Tarih
2008
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Ailevi Akdeniz Ateşi (AAA) bazı etnik gruplarda daha sık görülen , otozamal resesif geçişli ,rekürren poliserozit, sinovit, ateş gibi klinik bulgularla giden ve amiloidoz gibi hayatı tehditeden bir komplikasyona neden olabilen, hayat konforunu bozan multisistemik bir hastalıktır.Hastalığın gen mutasyonları ile ilişkisi gösterilmiş, farklı genotiplerde ve etnik gruplarda farklıseyir izleyebileceği sonucuna varılmıştır.Çalışmamızda 36'sı erkek , 53'ü kadın 89 Ailevi Akdeniz Ateşi (AAA) tanılı hasta çalışmayaalındı. Çalışmada hastaların klinik özellikleri ile MEFV geni tam DNA sekans analizi sonuçlarıkarşılaştırıldı. Gen analiz sonuçlarında, ekson 2,3,ve 5 te yer alan, klinikle ilişkisi iyi bilinmeyenmutasyon ve polimorfizmler, klasik mutasyonlardan daha sık bulundu. Klasik homozigotmutasyonu içeren grupta (grup I) hastalık ağırlık skoru, artrit oranları, amiloidoz oranı, erkenbaşlangıçlı hastalık anlamlı bir şekilde yüksek bulunmuştur. Sadece klasik tek heterozigotmutasyon içeren grupta (grup II) ve klasik birleşik heterozigot grupta (grup III) klinik özellikleraçısından anlamlı sonuç saptanmamakla birlikte, AAA hastalığının özelliklerini taşımaktadırlar.Klasik mutasyon dışında , klinikle ilişkisi iyi bilinmeyen polimorfizmler ve mutasyonları içerengrupta (grup IV) karın ağrısı, diğer üç gruptaki hasta grubumuza göre daha yüksek bulunmuşturve hepsi AAA kliniğini yansıtmaktadırlar. Bu grupta amiloidoz % 25 (n=3) oranında ve hastalıkağırlık skor ortalaması yüksek (skor:6,25) saptanmıştır. M694V homozigot , ilişkisi iyibilinmeyenlerden D102D, G138G, A165A homozigot polimorfizmi ve R202Q homozigotmutasyonlarının amiloidoz ile ilişkisi anlamlı bulmuştur. Amiloidozlu 15 hastamızın 9'undaM694V homozigot mutasyonu bulunmakta ve bunların hepisinde D102D , G138G, A165Ahomozigot polimorfizmi ve R202Q homozigot mutasyonuda saptanmıştır. Bu polimorfizmlerinamiloidozla ilişkisi, literatürde az miktardaki yayınla desteklenmektedir. Amiloidozluhastalarının hepsinin kolşisini düzenli olarak kullandığı öğrenilmiştir. En yüksek ortalamahastalık ağırlık skoru, amiloidozla ilişkili bu mutasyonlara homozigot sahip hastalarda [M694V(skor=9) ve R202Q (skor= 7,5)] saptanmıştır. Amiloidozlu hastalar ayrıca değerlendirildiğinde;literatürle uyumlu olarak , erken başlangıçlı hastalık, yüksek artrit oranları ve ailede amiloidozöyküsü istatistiksel olarak anlamlı bulunmuştur.Sonuç olarak grup II ve grup IV'ün AAA kliniğini yansıtması, grup IV'ün hastalık ağırlıkskorunun yüksek olması, 3 hastada amiloidoz gelişmesi ve ayrıca mutasyonlar ayrı olarakdeğerlendirildiğinde; amiloidozlu hastalarda M694V ile beraber bu polimorfizmlerin de beraberolması bu ilişkisi iyi bilinmeyen polimorfizm ve mutasyonların çokta masum olmadıklarınıgöstermiştir.Özellikle grup II ve grup IV hasta popülasyonuna uyan hastalarda tedavi kararı veamiloidoz gelişim riski açısından yakın izlem için MEFV geni tam DNA sekans analizi yapılmasıfaydalı olacağı görülmüştür. Ancak bunun daha geniş serilerle açıklıkla ortaya konmasıgerekmektedir
Familial Mediterranean Fever (FMF) is a multisystematic disease which is seen morefrequently in some ethnical groups, has an autosomal recessive transmission, progresses withsuch findings as recurrent polyserositis, synovitis and fever and causes a life-threateningcomplication such as amyloidosis and may impair the quality of life. Disease has been shown tohave a relationship with gene mutations and it was concluded that it may follow a distinct coursein different genotypes and ethnical groups.A total of 89 patients (36 males, 53 women) who received diagnose of FamilialMediterranean Fever (FMF) were included in our study. In the study, their clinic characteristicsand the results of MEFV gene full DNA sequence analysis were compared. Mutation andpolymorphisms with not well-known clinical relationships were found more often than classicalmutations in gene analysis results. In the group containing classical homozygote mutation (groupI), the disease severity score, arthritis rates, amyloidosis rate and disease with early onset werefound significantly higher. Although, significant results in terms of clinical characteristics havebeen obtained only in the group containing classical single heterozygote mutation (group II) andin classical combined heterozygote group (group III), they possessed the features of the FMFdiseases. In the group containing mutation and polymorphisms with not well-known clinicalrelationships, other than the classical mutation, (group IV) an increased abdominal pain wasfound compared to general patient population and they all reflected the FMF clinic. In this groupthe amyloidosis rate of 25 % (n=3) and the mean disease severity score of 6.25 were established.When the mutations were evaluated separately rather than as a group, a significant relationshipwas found between amyloidosis and the M694V homozygote (among the classical mutations);D102D, G138G, A165A homozygote polymorphism and R202Q homozygote mutation (amongthose with not well-known clinical relationships). In 9 of our 15 amyloidosis patients there was aM694V homozygote mutation and all of them had D102D, G138G, A165A homozygotepolymorphism and R202Q homozygote mutation. When the effects of the mutations on theseverity score were evaluated it was observed that the relationships of these polymorphisms withamyloidosis were supported by a small number of publications in the literature. It was discoveredthat all of the amyloidosis patients used their colchicine regularly. Among the patients havingthese amyloidosis-related mutations, the highest mean disease severity scores were found in thosehaving M694V (score=9) and R202Q (score=7.5) homozygote mutations. When patients withamyliodosis were evaluated separately, in consistent with the literature, the disease with earlyonset, higher arthritis rates and familial amyloidosis history were found statistically significant.Consequently, reflection of FMF clinic by group III and group IV, possession of higherdisease severity score by group IV, development of amyloidosis in three patients and in addition,when the mutations are evaluated separately, coexisting of M694V and these polymorphisms inpatients with amyloidosis, have been shown that these polymorphisms and mutations having notwell-known relationships are not that much innocent. It is considered that especially in patientswho meet group III and IV patient populations, to perform a MEFV gene full DNA sequenceanalysis for a closer follow-up would be helpful in terms of therapeutic decisions and risk fordevelopment of amyloidosis. However, this should be clearly suggested by larger series.
Familial Mediterranean Fever (FMF) is a multisystematic disease which is seen morefrequently in some ethnical groups, has an autosomal recessive transmission, progresses withsuch findings as recurrent polyserositis, synovitis and fever and causes a life-threateningcomplication such as amyloidosis and may impair the quality of life. Disease has been shown tohave a relationship with gene mutations and it was concluded that it may follow a distinct coursein different genotypes and ethnical groups.A total of 89 patients (36 males, 53 women) who received diagnose of FamilialMediterranean Fever (FMF) were included in our study. In the study, their clinic characteristicsand the results of MEFV gene full DNA sequence analysis were compared. Mutation andpolymorphisms with not well-known clinical relationships were found more often than classicalmutations in gene analysis results. In the group containing classical homozygote mutation (groupI), the disease severity score, arthritis rates, amyloidosis rate and disease with early onset werefound significantly higher. Although, significant results in terms of clinical characteristics havebeen obtained only in the group containing classical single heterozygote mutation (group II) andin classical combined heterozygote group (group III), they possessed the features of the FMFdiseases. In the group containing mutation and polymorphisms with not well-known clinicalrelationships, other than the classical mutation, (group IV) an increased abdominal pain wasfound compared to general patient population and they all reflected the FMF clinic. In this groupthe amyloidosis rate of 25 % (n=3) and the mean disease severity score of 6.25 were established.When the mutations were evaluated separately rather than as a group, a significant relationshipwas found between amyloidosis and the M694V homozygote (among the classical mutations);D102D, G138G, A165A homozygote polymorphism and R202Q homozygote mutation (amongthose with not well-known clinical relationships). In 9 of our 15 amyloidosis patients there was aM694V homozygote mutation and all of them had D102D, G138G, A165A homozygotepolymorphism and R202Q homozygote mutation. When the effects of the mutations on theseverity score were evaluated it was observed that the relationships of these polymorphisms withamyloidosis were supported by a small number of publications in the literature. It was discoveredthat all of the amyloidosis patients used their colchicine regularly. Among the patients havingthese amyloidosis-related mutations, the highest mean disease severity scores were found in thosehaving M694V (score=9) and R202Q (score=7.5) homozygote mutations. When patients withamyliodosis were evaluated separately, in consistent with the literature, the disease with earlyonset, higher arthritis rates and familial amyloidosis history were found statistically significant.Consequently, reflection of FMF clinic by group III and group IV, possession of higherdisease severity score by group IV, development of amyloidosis in three patients and in addition,when the mutations are evaluated separately, coexisting of M694V and these polymorphisms inpatients with amyloidosis, have been shown that these polymorphisms and mutations having notwell-known relationships are not that much innocent. It is considered that especially in patientswho meet group III and IV patient populations, to perform a MEFV gene full DNA sequenceanalysis for a closer follow-up would be helpful in terms of therapeutic decisions and risk fordevelopment of amyloidosis. However, this should be clearly suggested by larger series.
Açıklama
Bu tezin, veri tabanı üzerinden yayınlanma izni bulunmamaktadır. Yayınlanma izni olmayan tezlerin basılı kopyalarına Üniversite kütüphaneniz aracılığıyla (TÜBESS üzerinden) erişebilirsiniz.
Anahtar Kelimeler
Genetik, Genetics, Romatoloji, Rheumatology
