The 3'UTR 188 C>T Polymorphism of the OLR1 Gene: Effects in Serum Oxidized LDL Levels and Metabolic Parameters in Patients with Coronary Artery Disease

Abstract

Aim: Oxidized LDL, which stimulates signaling pathways that activate inflammatory reactions in endothelial cells during atherosclerosis, is defined as an important pathogenic factor in the development of cardiovascular diseases. The oxidized LDL receptor (LOX-1), which is the main receptor for oxidized LDL in endothelial cells, has the ability to specifically bind, internalize and degrade oxidized LDLs in endothelial cells. In this study, it was aimed to investigate the effect of 3'UTR188C>T polymorphism in the OLR1 gene encoding LOX-1 on serum oxidized LDL and lipid levels in the study groups consisting of coronary artery disease (CAD) patients and healthy controls, and to determine its relationship with lipid parameters in patients with CAD. Methods: Polymerase Chain Reaction and Restriction Fragment Length Polymorphism methods were used to detect the OLR1 gene 3'UTR188C>T polymorphism in groups of 50 CAD patients and 34 healthy controls. Statistical analyzes were performed with SPSS 20.0. Results: In the CAD group, oxidized LDL (p<0.001), total-cholesterol (p=0.020), Body Mass Indeks (BMI) (p=0.015), systolic (p<0.001) and diastolic (p=0.002) blood pressure levels and smoking frequency p=0.002) were higher, and serum HDL-C levels (p<0.001) were lower compared to healthy controls. OLR1 3'UTR188C>T genotype and allele distributions were found to be similar between the groups (p>0.05). The 188T allele was associated with higher oxidized LDL levels in both CAD (p<0.001) and control (p=0.013) groups. Patients with the 188TT genotype had high oxidized LDL (p<0.001), total cholesterol, LDL-cholesterol, triglyceride, and VLDL-cholesterol levels. Similarly, in healthy controls, the 188TT genotype was associated with high oxidized LDL, total- and LDL-cholesterol, triglyceride, VLDL-cholesterol, systolic blood pressure, and low serum HDL-cholesterol. Conclusion: Our findings indicate that the OLR1 3'UTR188C>T polymorphism may be associated with the development of CAD with its effects in favor of both serum oxidized LDL, which is a proatherogenic molecule, and an atherogenic lipid profile.

Keywords

• Oxidized LDL
• LOX-1
• OLR1
• gene
• lipid
• coronary artery disease

OLR1 Geni 3’UTR 188 C>T Polimorfizmi: Koroner Arter Hastalarında Serum Okside LDL Düzeylerine ve Metabolik Parametrelere Etkileri

Abstract

Amaç: Ateroskleroz sürecinde endotelyal hücrelerde enflamatuvar tepkimeleri aktive eden sinyal yolaklarını uyaran okside LDL, kardiyovasküler hastalıkların gelişiminde önemli bir patojenik faktör olarak tanımlanmaktadır. Endotel hücrelerinde okside LDL için başlıca reseptör olan okside LDL reseptörü (LOX-1), okside LDL’leri endotel hücrelerinde özgül olarak bağlayabilme, hücre içine alabilme ve degrade edebilme özelliğine sahiptir. Bu çalışmada LOX-1’i kodlayan OLR1 geninde 3’UTR188C>T polimorfizminin koroner arter hastaları ve sağlıklı kontrollerden oluşan çalışma gruplarında serum okside LDL ve lipid düzeylerine etkisinin araştırılarak KAH hastalarında lipid parametrelerle ilişkisinin belirlenmesi amaçlanmıştır. Yöntem: Çalışmaya katılan 50 KAH hastası ve 34 sağlıklı kontrolden oluşan gruplarda OLR1 geni 3’UTR188C>T polimorfizminin tespiti için Polimeraz Zincir Reaksiyonu ve Restriksiyon Fragman Uzunluk Polimorfizmi yöntemleri kullanılmıştır. İstatistiksel analiz SPSS 20.0 ile yapılmıştır. Bulgular: KAH grubunda okside LDL (p<0,001), total-kolesterol (p=0,020), Beden Kütle İndeksi (BKİ) (p=0,015), sistolik (p<0,001) ve diastolik (p=0,002) kan basıncı değerleri ve sigara kullanım sıklığı (p=0,002) sağlıklı kontrollere kıyasla yüksek ve serum HDL-K düzeyi düşük gözlenmiştir (p<0,001). OLR1 3’UTR188C>T genotip ve allel dağılımları gruplar arasında benzer bulunmuştur (p>0,05). 188T alleli hem KAH (p<0,001) hem de kontrol (p=0,013) gruplarında yüksek okside LDL düzeyleri ile ilişkili gözlenmiştir. 188TT genotipi taşıyan hastalarda okside LDL (p<0,001), total-kolesterol, LDL-kolesterol, trigliserid ve VLDL-kolesterol düzeyleri yüksekti. Benzer şekilde sağlıklı kontrollerde de 188TT genotipi yüksek okside LDL, total ve LDL-kolesterol, trigliserid, VLDL-kolesterol, sistolik kan basıncı ve düşük serum HDL-kolesterol düzeyi ile ilişkiliydi. Sonuç: Bulgular OLR1 3’UTR 188 C>T polimorfizminin hem proaterojenik bir molekül olan serum okside LDL hem de aterojenik lipid profili lehine etkileriyle KAH gelişimiyle ilişkili olabileceğine işaret etmektedir.

Keywords

• Okside LDL
• LOX-1
• OLR1
• gen
• lipid
• koroner arter hastalığı

Supporting Institution

Yazarlar finansal destek almadıklarını beyan ederler.

Thanks

Makale yazarları İstanbul Üniversitesi Sağlık Bilimleri Enstitüsü’ne destekleri için teşekkür eder.

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