The Effects of the SHBG Gene (TAAAA)n Pentanucleotıde Repeats Numbers on Serum SHBG and Lipid Levels in Men with Coronary Heart Disease

Yıl 2017, Sayı: 3, 174 - 192, 30.12.2017

Özlem Kurnaz Gömleksiz , Başak Akadam Teker Zehra Buğra , Beyhan Ömer , Hülya Yılmaz Aydoğan

Öz

Aim: One of
the important regulators of the High-Density Lipoprotein Cholesterol (HDL-C) is
sex hormones. Sex hormone binding globulin (SHBG) is a determining factor for
the bioactive free sex hormones. Serum
SHBG concentration is positively associated with HDL-C levels and under the
genetic control. A (TAAAA)n pentanucleotide repeats polymorphism (rs35785886)
was identified in Alu sequence in 5’ promotor of human SHBG gene. A
correlation has been reported between repeat numbers and blood SHBG
concentrations. In the present study, our
aim was to investigate the (TAAAA)n pentanucleotide repeat polymorphism and its
association with SHBG protein and HDL-C levels in Turkish men with Coronary
Heart Disease (CHD).

Method:
SHBG (TAAAA)n pentanucleotide repeat polymorphism was studied by
polyacrylamide gel electrophoresis
after polymerase chain reaction (PCR) in 75 men with CHD and 50 healthy men in
Turkish population. Serum SHBG levels were measured by
electro-chemiluminescence method.

Findings: The frequency
of (TAAAA) six repeats allele was higher in controls (p=0.002, GR:0.293 (95%
CI=0.133-0.649)). In control group without six repeats allele, serum
triglyceride levels were higher than in controls with six repeats allele
(p=0.048). While serum SHBG levels were higher in short repeat (≤ 8 repeats)
allele carriers (p=0.006) in control group, serum SHBG levels were higher in
patients with six repeat allele (p=0.027). HDL-C/LDL-C ratio (p=0.027) and mean
systolic blood pressure (p=0.008) were observed higher in patients with 8
repeat allele compared to patients without 8 repeat allele. There
was a significant decrease in serum SHBG by the smoking effect in long-repeat
allele carriers in CHD group (p=0.024).

Conclusion: SHBG
(TAAAA) 6 repeats-allele in CHD group and short repeats (≤ 8 repeats)  in control group were in a remarkable
association with high SHBG levels. Our findings suggest that there is a
positive association between SHBG levels and HDL-C levels in the CHD group and
this association may be affected by the SHBG (TAAAA)n polymorphism and the
effects of an interaction between repeat numbers and smoking.

Anahtar Kelimeler

Coronary heart disease, sex hormone binding globulin, TAAAA pentanucleotide repeat polymorphism

Koroner Kalp Hastası Erkeklerde SHBG Geni (TAAAA)n Pentanükleotid Tekrar Sayılarının Serum SHBG ve Lipid Düzeyleri Üzerine Etkisi

Öz

Amaç:
Yüksek yoğunluklu lipoprotein-kolesterol (HDL-K) seviyelerinin önemli
düzenleyicilerinden biri cinsiyet hormonlarıdır. Cinsiyet hormon bağlayıcı globülin
(SHBG), biyoaktif serbest cinsiyet hormonlarını belirleyen bir faktördür. Serum
SHBG konsantrasyonu HDL-K düzeyleri ile pozitif ilişkilidir ve kısmen genetik
kontrol altındadır. İnsan SHBG geninin 5’ promotöründe bir Alu dizisi içinde
(TAAAA)n pentanükleotid tekrar polimorfizmi (rs35785886) tanımlanmıştır. Tekrar
sayısı ve serum SHBG konsantrasyonları arasında korelasyon olduğu
bildirilmiştir. Bu çalışmada koroner kalp hastalığı (KKH) olan Türk
erkeklerinde SHBG geni pentanükleotid (TAAAA)n tekrar polimorfizminin serum
SHBG proteini ve HDL-K düzeyleriyle ilişkisinin incelenmesi amaçlanmıştır.

Yöntem:
SHBG geni (TAAAA)n pentanükleotid tekrar polimorfizmi 75 KKH erkek ve 50
sağlıklı erkekte polimeraz zincir reaksiyonu (PZR) sonrası Poliakrilamid jel
elektroforezi yöntemiyle belirlenmiştir. Serum SHBG düzeyleri
Elektrokemilüminesan metoduyla ölçülmüştür.

Bulgular: Kontrol
grubunda 6 TAAAA tekrar allel frekansı KKH grubuna göre yüksektir (p=0,002
GR:0,293 (%95 GA= 0,133-0,649)). Kontrol grubunda 6 tekrar
alleli taşımayanlarda serum trigliserid düzeyi 6 tekrar taşıyanlara göre yüksek
gözlenmiştir (p=0,048). Kısa tekrar allellerini (≤ 8 tekrar) taşıyan
kontrollerde serum SHBG düzeyi yüksek iken (p=0,006), hasta grubunda 6 tekrar
taşıyan bireylerde serum SHBG düzeyi yüksektir (p=0,027). 8 tekrar alleli olan
hastalarda 8 tekrar alleli bulunmayanlara göre HDL-K/LDL-K oranı (p=0,027) ve
sistolik kan basıncı (p=0,008) düzeyleri düşük gözlenmiştir. KKH grubunda uzun
tekrar alleli taşıyanlarda sigara etkisiyle birlikte serum SHBG seviyelerinde
anlamlı bir düşüş belirlenmiştir (p=0,024).

Sonuç: KKH
grubunda SHBG (TAAAA) 6 tekrar alleli ve kontrollerde ise kısa tekrarlar (≤ 8
tekrar) yüksek SHBG düzeyleriyle kayda değer bir ilişki içindedir. KKH
grubumuzda SHBG düzeyleriyle HDL-K düzeyleri arasında pozitif ilişki
bulunmuştur ve bu ilişkinin SHBG (TAAAA)n polimorfizminden ve tekrar sayısının
sigara kullanımı ile birlikte olan etkisinden etkilenebileceği düşünülmüştür.

Anahtar Kelimeler

Koroner kalp hastalığı, cinsiyet hormonu bağlayıcı globülin, TAAAA pentanükleotid tekrar polimorfizmi

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