TY  - JOUR
T1  - The Role of 21-Hydroxylase Deficiency in The Pathogenesis of Behçet Disease
TT  - Behçet Hastalığı Patogenezinde 21-Hidroksilaz Eksikliğinin Rolü
AU  - Gül, Nurdan
AU  - Gül, Ahmet
AU  - İnanç, Murat
AU  - Öçal, Lale
AU  - Aral, Orhan
AU  - Alagöl, Faruk
PY  - 2018
DA  - March
DO  - 10.18017/iuitfd.390041
JF  - Journal of Istanbul Faculty of Medicine
JO  - İst Tıp Fak Derg
PB  - Istanbul University
WT  - DergiPark
SN  - 1305-6441
SP  - 11
EP  - 16
VL  - 81
IS  - 1
LA  - en
AB  - Objective: Acne-like skin lesions and moresevere disease course in males suggest a role for sex hormones in thepathogenesis of Behçet disease (BD). HLA-B51 is the main genetic susceptibilityfactor for BD, and CYP21A2 gene responsible for most of congenital adrenalhyperplasia (CAH) is located within the MHC locus on chromosome 6p21.3. Weaimed to investigate the possible role of 21-hydroxylase deficiency in linkagedisequilibrium with HLA-B51 and causing androgen excess.Materials and Methods: We studied 18healthy controls, 29 BD patients and 15 patients with ankylosing spondylitis(AS). All subjects underwent ACTH stimulation test. Basal and stimulated serumcortisol and 17-OH-progesterone (17-OH-P) levels and basaldehydroepiandrosterone sulfate (DHEA-S), total testosterone and sex hormonebinding globulin (SHBG) levels were measured.Results: According to current guidelines,we accepted 10 ng/mL as the cut-off point for 17-OH-P to define non-classic CAH(NCAH). After ACTH stimulation 3 of BD patients (10.3%) and 5 AS patients(33.3%) had high 17-OH-P concentrations. Those individuals were considered asNCAH or possible carriers for CAH mutations. Three out of 8 BD patients withprominent acne were identified as NCAH biochemically. Mean total testosteronelevels of BD patients were significantly lower than those of healthy controls,however these levels were normal in BD patients with high 17-OH-P.Conclusion: This preliminary workdocumented high 17-OH-P levels following ACTH stimulation in a subset of BD andAS patients, and genetic studies are necessary to investigate the role of21-hydroxylase deficiency in association with HLA-B alleles in theirpathogenesis.
KW  - 21-hydroxylase deficiency
KW  - Behçet disease
KW  - Ankylosing spondylitis
KW  - HLA-B51
KW  - HLA-B27
KW  - CYP21A2 gene
N2  - Amaç: Akne benzeri deri lezyonlarının sıklığıve hastalığın erkeklerde daha ağır seyretmesi Behçet hastalığı (BH)patogenezinde seks hormonlarının rolünün olabileceğini düşündürmektedir.HLA-B51 BH için en önemli genetik duyarlılık faktörüdür. Konjenital adrenalhiperplazilerin (KAH) çoğundan sorumlu olan CYP21A2 geni kromozom 6p21.3’dekiMHC bölgesinde yerleşimlidir. Bu çalışmada CYP21A2 genindeki olası bazımutasyonların HLA-B51 ile bağlantı dengesizliği göstererek 21-hidroksilazeksikliğine ve bunun sonucunda androjen fazlalığına yol açarak BH patogenezinekatkı yapabileceği hipotezini araştırmayı amaçladık.Gereç ve Yöntem: Çalışma grubunu 18 sağlıklıkontrol, 29 BH olan hasta ve 15 ankilozan spondilit (AS) hastası oluşturdu.Bütün hastalara ACTH uyarı testi yapıldı. Bazal ve ACTH uyarısı sonrası serumkortizol ve 17-OH-progesteron (17-OH-P) düzeyleri ve bazaldehidroepiandrosteron sülfat (DHEA-S), total testosteron ve seks hormonu bağlayıcıglobulin (SHBG) düzeyleri ölçüldü.Bulgular: Kılavuzların önerdiği şekilde,klasik olmayan KAH tanısı için 17-OH-P için eşik değer olarak 10 ng/mL alındı.ACTH uyarısı sonrası 3 BH (%10,3) ve 5 AS hastasının (%33,3) 17-OH-P düzeyleriyüksek bulundu. Bu hastaların klasik olmayan KAH hastaları ya da KAHmutasyonları için taşıyıcı olabileceği düşünüldü. Belirgin aknesi olan 8 BH’danüçünün biyokimyasal değerleri klasik olmayan KAH ile uyumluydu. BH olanlarınortalama total testosteron düzeylerinin sağlıklı kontrollerinkinden anlamlıolarak düşük olduğu görüldü. Bununlabirlikte 17-OH-P düzeyi yüksek olan hastalarda testosteron düzeyleri normaldi.Sonuç: Bu pilot çalışmada BH ve AS hastalarınınbir grubunda ACTH uyarısı sonrası yüksek 17-OH-P değerleri gözlemledik.Bulgularımız HLA-B allelleri ile bağlantı dengesizliği gösteren olası21-hidroksilaz eksikliğinin patogeneze katkısının olabileceğini düşündürmekteve verilerin genetik çalışmalarla doğrulanmasını gerektirmektedir.
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UR  - https://doi.org/10.18017/iuitfd.390041
L1  - https://dergipark.org.tr/en/download/article-file/453622
ER  -