Özlem KURNAZ GÖMLEKSİZ, Başak AKADAM TEKER, Zehra BUĞRA, Beyhan ÖMER, Hülya YILMAZ AYDOĞAN

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

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

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

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.

Keywords:

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

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