Turkiye Klinikleri Journal of Internal Medicine

.: REVIEW
Sarkoidoz Etiyolojisinde Genetik ve Çevresel Faktörlerin Etkisi
The Effect of Genetics and Environmental Factors in Sarcoidosis Etiology
Engin AYNACIa, Burçin ERKALb,d, Ceyda HAYRETDAĞc,d, Büşra ALATLId, Gamze YILDIZd, Ayşegül ARSLANELd, Ender COŞKUNPINARb,d
aGöğüs Hastalıkları Kliniği, Memorial Bahçelievler Hastanesi,
bTıbbi Biyoloji AD,
cAnatomi AD,
dSağlık Bilimleri Üniversitesi Tıp Fakültesi, İstanbul, TÜRKİYE
Turkiye Klinikleri J Intern Med. 2019;4(2):92-8
doi: 10.5336/intermed.2019-65004
Article Language: TR
Full Text
ÖZET
 Sarkoidoz, etiyolojisi bilinmeyen sistemik bir granülomatöz hastalıktır. Sarkoidozda granülomatöz inflamasyon; santral sinir sistemi, deri, göz ve en çok da solunum sistemi olmak üzere birçok organı etkileyebilmekte, ciddi morbidite ve mortaliteye neden olmaktadır. Sarkoidozun patofizyolojisinde tek bir ana gen veya yolak sorumlu değildir. Bunun yerine, birlikte çalışan çoklu genetik ve çevresel faktörlerden kaynaklanan karmaşık bir yapısı vardır. Bu kompleks yapı, hastalığın genel mekanizmasının anlaşılmasını güçleştirmektedir. Ayrıca ailesel vakaların incelenmesiyle de hastalığın kalıtımsal bir geçiş sergileyebildiği ve hatta monozigot ikizlerde, dizigotik ikizlere oranla sarkoidoz oluşum riskinin çok daha fazla olduğu bilinmektedir. Aday gen araştırmalarında bazı lokuslar belirlenmiş ve bu lokusların sarkoidoz oluşum riskini artırdığı ifade edilmiştir. Sarkoidoz oluşumunda bir diğer önemli role sahip olan yapı ise bağışıklık sisteminde yer alan faktörlerdir. Özellikle insan lökosit antijenlerinin yapısı ve T-hücrelerinin aktivasyonu hastalığın immünopatogenezinde ön plana çıkmaktadır. Hastalığın epidemiyolojisi ülkeden ülkeye farklılık göstermekte ve görülen klinik bulgular da etnik kökenlere göre değişmektedir. Bu çalışmada, sarkoidozun oluşum sürecinde etkili olduğu düşünülen genetik ve çevresel faktörler ele alınmıştır. İlerleyen teknolojiyle beraber; çalışılan hasta gruplarının artırılması ve yapılacak tüm genom dizilemelerinin analizlerine bağlı olarak yeni gen adaylarının tespiti, hastalığın tanı ve tedavi sürecindeki biyobelirteçlerin ortaya çıkarılması ve bulunacak yeni tedavi yollarının geliştirilmesi sarkoidoz hastaları için önemli bir umut kaynağı olacaktır.

Anahtar Kelimeler: Sarkoidoz; genetik; çevresel faktörler
ABSTRACT
 Sarcoidosis is a systemic granulomatous disease of unknown etiology. Granulomatous inflammation in sarcoidosis can affect many organs including central nervous system, skin, eye and most of the respiratory system and these organs are leading to serious morbidity and mortality. A single major gene or pathway is not responsible of pathophysiology of sarcoidosis. Instead, it has a complex structure that results from multiple genetic and environmental factors that work together. This complex structure makes it difficult to understand the general mechanism of the disease. In addition, it is known that the disease can exhibit an inherited transition with familial cases and the risk of sarcoidosis of monozygotic twins is much higher than dizygotic twins. Some loci were identified in candidate gene studies and it was stated that these loci increase the risk of sarcoidosis. Another important role in the formation of sarcoidosis belongs to immune system factors. In particular, the structure of human leukocyte antigens and activation of T cells are prominent in the immunopathogenesis of the disease. The epidemiology of the disease varies among countries according to the ethnic background in clinical findings. In this review, genetic and environmental factors that are thought to be effective in the formation of sarcoidosis are discussed. Depending on whole genome sequencing and increase in the number of patients, new candidates will be detected and the biomarkers in the diagnosis and treatment process of the disease will be identified. Therefore, it is promising for the development of new treatment methods for patients with sarcoidosis.

Keywords: Sarcoidosis; genetics; environmental factors
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