Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
Koroner Kalp Hastalarında PPARG ve PPAR-B/D Gen Varyasyonlarının Serum LDL Alt-fraksiyonlarına Etkilerinin İncelenmesi
Study on the Effects of PPARG and PPAR-B/D Gene Variations on Serum LDL Subfractions in Patients with Coronary Heart Disease
Deniz KANCAa,b, Bengü TOKATa, Zehra BUĞRAc, Uzay GÖRMÜŞd, Oğuz ÖZTÜRKa, Hülya YILMAZ AYDOĞANa
aMoleküler Tıp AD, İstanbul Üniversitesi Aziz Sancar Deneysel Tıp Araştırma Enstitüsü,
bMoleküler Biyoloji ve Genetik Bölümü, Haliç Üniversitesi Fen-Edebiyat Fakültesi,
c Kardiyoloji AD, İstanbul Üniversitesi İstanbul Tıp Fakültesi,
dBiyokimya AD, İstanbul Bilim Üniversitesi Tıp Fakültesi, İstanbul
Turkiye Klinikleri J Med Sci. 2017;37(1):1-9
doi: 10.5336/medsci.2016-53704
Article Language: TR
Full Text
ÖZET
 Amaç: Son yıllarda yapılan çalışmalarda lipoprotein alt fraksiyonlarından büyük-LDL'nin antiaterojenik, küçükyoğun LDL'nin (sdLDL) aterojenik olduğu ve tüm LDL alt fraksiyonlarının karakterinin aynı şekilde aterojenik olmadığı gözlenmiştir. Peroksizom-Proliferatör Aktive Reseptör (PPAR) beta/delta (PPAR-B/D) ve gama (PPARG) genlerindeki sekans değişimlerinin serum lipid düzeyleriyle ilişkili oldukları bilinmektedir. Ancak lipoprotein alt fraksiyonları üzerindeki etkileri kesin değildir. Bu çalışmanın amacı, söz konusu genetik varyasyonlarla serum LDL alt fraksiyonları arasındaki olası ilişkinin koroner kalp hastalığı (KKH)'nda ve normolipidemik kontrollerde incelenmesi hedeflenmiştir. Gereç ve Yöntemler: Çalışmamızda İstanbul Üniversitesi Kardiyoloji AD tarafından 2008-2009 yılları arasında takip edilen 58 KKH tanılı statin tedavisi almakta olan hastada ve 63 sağlıklı kontrolde PPARG ve PPAR-B/D genlerine ait varyasyonlar PZR-RFUP tekniği ile incelendi. Serum lipid düzeyleri enzimatik yöntemle ölçüldü. LDL alt tiplemesi Lipoprint Sistemi (Quantimetrix, CA, USA) ile gerçekleştirildi. İstatistiksel analiz SPSS 20.0 paket programı ile yapıldı. Bulgular: PPARG P12A (rs1801282) ve PPAR-B/D +294T/C (rs52016520) varyasyonlarının çalışma gruplarındaki dağılımı benzerdir (p>0.05). PPARG C161T (rs3856806) CC genotip frekansı KKH hasta grubunda yüksektir (p=0.029). Serum LDL alt fraksiyonları sadece P12A varyasyonundan etkilenmiştir. Kontrol grubunda PPARG P12A heterozigot ProAla genotipi yüksek büyük-LDL alt fraksiyonu ile ilişkili iken (p=0.024), homozigot ProPro genotipi yüksek HDL-kolesterol düzeyleri ile ilişkilidir (p=0.033). KKH grubunda PPARG P12A normal ProPro genotipi yüksek triaçilgliserol ve LDL-kolesterol (LDL-K) düzeyleri (sırasıyla p=0.031 ve p=0.010) ve PPAR-B/D +294T/C minör C alleli yüksek LDL-K düzeyleri ile ilişkili bulunmuştur (p=0.038). KKH grubunda ise, PPARG P12A varyasyonunun lipoprotein alt fraksiyon düzeylerine etkisi bulunmamıştır. Sonuç: KKH hastalarında PPARG-P12A ve PPAR-B/D +294T/C varyasyonlarının serum LDL-K düzeylerinde etkili iken LDL alt fraksiyon dağılımında etkili olmadıkları ve normolipidemik sağlıklı bireylerde ise alt fraksiyon dağılımında etkili oldukları tespit edilmiştir. Sonuç olarak, PPAR gen varyasyonlarının lipid ve LDL alt fraksiyonları üzerindeki etkilerinin kardiyometabolik durumdan etkilendiği söylenebilir.

Anahtar Kelimeler: PPAR gama; PPAR-beta; genler; lipoproteinler; LDL
ABSTRACT
 Objective: Recently, it was observed that while large-buoyant low density lipoprotein (LDL) subfractions have an antiatherogenic character, small-dense LDL (sdLDL) subfractions have an atherogenic character and thus not all LDL subfractions have the same atherogenic character. It is shown that DNA sequence changes in Peroxisome Proliferator-Activated Receptor (PPAR) beta/delta (PPAR-B/D) and gamma (PPARG) genes affect lipid profile. Little is known about the effects of the PPAR variations on LDL subfractions. Purpose of the present study was to examine the presence of a potential association between aforementioned genetic variations and serum LDL subfractions in patients with coronary heart disease (CHD) and in normolipidemic controls. Material and Methods: This study comprised 63 healthy controls and 58 patients with coronary heart disease receiving statin therapy, attending the Department of Cardiology, Istanbul University School of Medicine in Istanbul between 2008 and 2009. The variations of the PPARG and PPAR-B/D genes were determined by PCR-RFLP technique. Serum lipid levels were measured enzymatically. The serum LDL subfractioning was carried out with the Lipoprint System (Quantimetrix, CA, USA). Statistical analyses was performed by SPSS for windows version 20.0. Results: The allelic and genotypic frequencies of the PPARG P12A (rs1801282) and PPARD +294T/C (rs52016520) variations were not different between the study groups (p>0.05), while PPARG C161T (rs3856806) CC genotype frequency was higher in the CHD patient group (p=0.029). The Serum LDL subfractions were observed to be only affected by the PPARG P12A variation. While PPARG P12A heterozygous ProAla genotype was associated with increased large-buoyant LDL subfractions (p=0.024), homozygous ProPro genotype was associated with high HDL cholesterol levels (p=0.033) in the control group. The PPARG Pro12Ala normal ProPro genotype was associated with increased triacylglycerol and LDL cholesterol levels (p=0.031 and p=0.010, respectively) and PPAR-B/D +294T/C minor C allele was associated with high LDL cholesterol levels (p=0.038) in the CHD group. There was no effect of the PPARG P12A variation on the lipoprotein subfractions in the CHD group. Conclusion:We observed that the PPARG Pro12Ala normal ProPro genotype and PPAR-B/D +294T/C minor C allele show a detrimental effect on serum LDL-K levels, while they are not effective on the distribution of LDL subfractions in the CHD patients. However, it was observed that the PPARG ProAla genotype contribute the antiatherogenic large-buoyant LDL subfraction in normolipidemic subjects. As a result, it is possible that the effects of genetic variations of the PPARs on lipid and LDL subfractions may have been affected by cardiometabolic circumstances.

Keywords: PPAR gamma; PPAR-beta; genes; lipoproteins, LDL

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