Behçet Hastalığı Patogenezinde 21-Hidroksilaz Eksikliğinin Rolü

Yıl 2018, Cilt: 81 Sayı: 1, 11 - 16, 12.03.2018

Nurdan Gül Ahmet Gül Murat İnanç Lale Öçal Orhan Aral Faruk Alagöl

https://doi.org/10.18017/iuitfd.390041

Öz

Amaç: Akne benzeri deri lezyonlarının sıklığı
ve hastalığın erkeklerde daha ağır seyretmesi Behçet hastalığı (BH)
patogenezinde seks hormonlarının rolünün olabileceğini düşündürmektedir.
HLA-B51 BH için en önemli genetik duyarlılık faktörüdür. Konjenital adrenal
hiperplazilerin (KAH) çoğundan sorumlu olan CYP21A2 geni kromozom 6p21.3’deki
MHC bölgesinde yerleşimlidir. Bu çalışmada CYP21A2 genindeki olası bazı
mutasyonların HLA-B51 ile bağlantı dengesizliği göstererek 21-hidroksilaz
eksikliğine ve bunun sonucunda androjen fazlalığına yol açarak BH patogenezine
katkı yapabileceği hipotezini araştırmayı amaçladık.

Gereç ve Yöntem: Çalışma grubunu 18 sağlıklı
kontrol, 29 BH olan hasta ve 15 ankilozan spondilit (AS) hastası oluşturdu.
Bütün hastalara ACTH uyarı testi yapıldı. Bazal ve ACTH uyarısı sonrası serum
kortizol ve 17-OH-progesteron (17-OH-P) düzeyleri ve bazal
dehidroepiandrosteron sülfat (DHEA-S), total testosteron ve seks hormonu bağlayıcı
globulin (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 düzeyleri
yüksek bulundu. Bu hastaların klasik olmayan KAH hastaları ya da KAH
mutasyonları için taşıyıcı olabileceği düşünüldü. Belirgin aknesi olan 8 BH’dan
üçünün biyokimyasal değerleri klasik olmayan KAH ile uyumluydu. BH olanların
ortalama total testosteron düzeylerinin sağlıklı kontrollerinkinden anlamlı
olarak düşük olduğu görüldü.  Bununla
birlikte 17-OH-P düzeyi yüksek olan hastalarda testosteron düzeyleri normaldi.

Sonuç: Bu pilot çalışmada BH ve AS hastalarının
bir grubunda ACTH uyarısı sonrası yüksek 17-OH-P değerleri gözlemledik.
Bulgularımız HLA-B allelleri ile bağlantı dengesizliği gösteren olası
21-hidroksilaz eksikliğinin patogeneze katkısının olabileceğini düşündürmekte
ve verilerin genetik çalışmalarla doğrulanmasını gerektirmektedir.

Anahtar Kelimeler

21-hidroksilaz eksikliği, Behçet hastalığı, Ankilozan spondilit, HLA-B51, HLA-B27, CYP21A2 geni

The Role of 21-Hydroxylase Deficiency in The Pathogenesis of Behçet Disease

Öz

Objective: Acne-like skin lesions and more
severe disease course in males suggest a role for sex hormones in the
pathogenesis of Behçet disease (BD). HLA-B51 is the main genetic susceptibility
factor for BD, and CYP21A2 gene responsible for most of congenital adrenal
hyperplasia (CAH) is located within the MHC locus on chromosome 6p21.3. We
aimed to investigate the possible role of 21-hydroxylase deficiency in linkage
disequilibrium with HLA-B51 and causing androgen excess.

Materials and Methods: We studied 18
healthy controls, 29 BD patients and 15 patients with ankylosing spondylitis
(AS). All subjects underwent ACTH stimulation test. Basal and stimulated serum
cortisol and 17-OH-progesterone (17-OH-P) levels and basal
dehydroepiandrosterone sulfate (DHEA-S), total testosterone and sex hormone
binding 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 as
NCAH or possible carriers for CAH mutations. Three out of 8 BD patients with
prominent acne were identified as NCAH biochemically. Mean total testosterone
levels 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 work
documented high 17-OH-P levels following ACTH stimulation in a subset of BD and
AS patients, and genetic studies are necessary to investigate the role of
21-hydroxylase deficiency in association with HLA-B alleles in their
pathogenesis.

Anahtar Kelimeler

21-hydroxylase deficiency, Behçet disease, Ankylosing spondylitis, HLA-B51, HLA-B27, CYP21A2 gene

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