Publication: Türk toplumunda düşük yüksek dansiteli lipoprotein-kolesterol düzeyi ve lesitin kolesterol asiltransferaz ilişkisinin gen ve protein düzeyinde araştırılması
Abstract
Lesitin Kolesterol Açil Transferaz (LCAT) kolesterol hemostazını sağlayan ve kanda taşınmasını düzenleyen anahtar enzimdir. LCAT’nin görevi yüksek dansiteli lipoprotein-kolesterol (HDL-K)’deki kolesterolü kolesteril esterlerine çevirerek dokulardan HDL’ye kolesterol hareketini sağlamaktır. Ayrıca kolesterol ters taşınmasında önemli bir enzim olarak plazmadan karaciğere kolesterol taşınmasını ve karaciğerdeki kolesterol yıkımını düzenler. HDL-K düzeyinin yanı sıra fonksiyonunun da önemli olduğu son çalışmalarda görülmüştür. Bu çalışmada lipid metabolizmasında Türkiye’de sık görülen ve iyi kolesterol olarak bilinen HDL-K’nin düşüklüğünün muhtemel sebeplerinden biri olan LCAT, gen ve enzim düzeyinde incelenmiştir. Çalışma için plazma HDL-K düzeyleri düşük (HDL-K 35) sağlıklı 50 kişi ve HDL-K düzeyleri yüksek (HDL-K 65) sağlıklı 50 kişi seçildi. Her iki gruba dahil bireylerde beden kütle indeksi (BKİ), sigara ve alkol tüketimi, aile hikayesi sorgulandı ve kan lipid profilleri incelendi. Çalışma RFLP genotiplemesi, LCAT enzim aktivitesi ve ELISA ile enzim düzeyi olmak üzere üç aşamalı olarak planlandı. İlk aşamada RFLP analizinde LCAT geninde Exon 4’te 511C/ T, Exon 5’te 608C/ T ve Exon 6’da 4886C/ T polimorfizmleri çalışıldı. LCAT enzim aktivitesi ve ELISA plazmada bakıldı. 4886C/ T ve 608C/ T polimorfizmleri Hardy Weinberg uyumluydu. Literatürden farklı olarak 4886 C/ T polimorfizmi HDL-K seviyeleriyle istatistiksel anlamlılığa sahipti (p=0.05). Diğer iki polimorfizmin HDL-K ile ilişkisi istatistiksel olarak anlamlı değildi. Literatür ile uyumlu olarak çalışmamızda LCAT aktivitesinin HDL seviyesi düşük grupta daha düşük (p=0.04), LCAT düzeylerinin de HDL seviyesi düşük gruplarda daha düşük (p=0.05) olduğu görülmektedir. Yeni bir bulgu, LCAT düzeyi ile TG (p=0.01) Total kolesterol (p=0.000), LDL (p=0.001) ve BKİ (p=0.000) arasında da pozitif ilişki bulunmasıydı. Çalışmamızda aktivite, enzim düzeyi ve genetik varyasyonun HDL fonksiyonu ve düzeyine ışık tutabileceği gösterilmiştir. Enzim aktivitesi, kolesterol, lipoprotein, polimorfizm
Lecithin cholesterol acyltransferase (LCAT) is one of the key enzymes controlling cholesterol hemostasis and transport. LCAT maintains cholesterol efflux from tissues by converting the cholesterol content of High Density Lipoprotein Cholesterol (HDL-C) to long chain cholesteryl esters. Furthermore it accentuates ‘reverse cholesterol transport’ from plasma to liver, and induces cholesterol degradation. LCAT enzyme is a potential cause for low HDL-C. LCAT may also modify HDL-C function. The aim of this study was to investigate whether LCAT polymorphisms, LCAT activity and mass separately or together had an effect on reverse cholesterol transport and low HDL-C. Healthy subjects (N=50) with high HDL-C levels (HDL-C>65) and subjects (n=50) with low HDL levels (HDL<35) were enrolled in this study. Standard risk factors such as smoking, alcohol consumption, family history and body mass index (BMI) were collected. The study analyzed LCAT gene polymorphisms, enzyme level and function. LCAT gene was analyzed for mutation by RFLP analysis. The genetic analysis involved 3 polymorphisms; 511C/ T in Exon4, 608 C/ T in Exon5 and 4886 C/ T in Exon6. Second step was measurement of LCAT activity based on a colorimetric method. The third step was measurement of LCAT mass by ELISA. Our results indicated the frequency of LCAT polymorphism 4886 C/ T was in accordance with Hardy Weinberg and associated with HDL levels (p=0.05). The level (p=0.045) and the activity (p=0.04) of the enzyme was associated with HDL levels (p=0.03). LCAT levels were correlated with TG (p=0.01), total cholesterol (p=0.000), LDL (p=0.001) and BMI (P=0.000). LCAT activtity together with the enzyme level and genetic variation on 4886C/ T may elucidate the role of HDL function. Key words: Enzyme activity, cholesterol, lipoprotein, polymorphism
Lecithin cholesterol acyltransferase (LCAT) is one of the key enzymes controlling cholesterol hemostasis and transport. LCAT maintains cholesterol efflux from tissues by converting the cholesterol content of High Density Lipoprotein Cholesterol (HDL-C) to long chain cholesteryl esters. Furthermore it accentuates ‘reverse cholesterol transport’ from plasma to liver, and induces cholesterol degradation. LCAT enzyme is a potential cause for low HDL-C. LCAT may also modify HDL-C function. The aim of this study was to investigate whether LCAT polymorphisms, LCAT activity and mass separately or together had an effect on reverse cholesterol transport and low HDL-C. Healthy subjects (N=50) with high HDL-C levels (HDL-C>65) and subjects (n=50) with low HDL levels (HDL<35) were enrolled in this study. Standard risk factors such as smoking, alcohol consumption, family history and body mass index (BMI) were collected. The study analyzed LCAT gene polymorphisms, enzyme level and function. LCAT gene was analyzed for mutation by RFLP analysis. The genetic analysis involved 3 polymorphisms; 511C/ T in Exon4, 608 C/ T in Exon5 and 4886 C/ T in Exon6. Second step was measurement of LCAT activity based on a colorimetric method. The third step was measurement of LCAT mass by ELISA. Our results indicated the frequency of LCAT polymorphism 4886 C/ T was in accordance with Hardy Weinberg and associated with HDL levels (p=0.05). The level (p=0.045) and the activity (p=0.04) of the enzyme was associated with HDL levels (p=0.03). LCAT levels were correlated with TG (p=0.01), total cholesterol (p=0.000), LDL (p=0.001) and BMI (P=0.000). LCAT activtity together with the enzyme level and genetic variation on 4886C/ T may elucidate the role of HDL function. Key words: Enzyme activity, cholesterol, lipoprotein, polymorphism