Department of Molecular Medicine, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
DNA Cell Biol. 2012 May;31(5):867-75. doi: 10.1089/dna.2011.1464. Epub 2012 Jan 25.
The aim of this study was to determine the role of polymorphic variants of apolipoprotein E (APOE) and peroxisome proliferator-activated receptor delta (PPARD) genes in the development of coronary heart disease (CHD), and the PPARD and APOE gene-gene interaction in a Turkish population. This study was carried out using a sample of 223 patients with CHD (103 with diabetes and 120 without diabetes) and 101 controls. PPARD +294T/C and APOE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism technique. The PPARD and APOE genotype distributions were the same between study groups (p>0.05). In the nondiabetic CHD patients, the PPARD +294 C allele showed higher serum low-density lipoprotein cholesterol (LDL-C) level than the common +294 TT homozygote genotype (3.83 ± 1.01 vs. 3.33 ± 1.14, p=0.015). In addition, a significant association between APOE 4 and PPARD +294 C alleles was detected based on their effects on LDL-C in the nondiabetic CHD patients (+294 C/APOE4: 4.43 ± 0.88 vs. +294 TT/nonAPOE 4: 3.48 ± 1.09, p = 0.009). This association indicated the interaction of two genes on plasma LDL-C levels ascended in the order +294 T<+294 T-APOE 4<+294 C<APOE 4<+294 C-APOE 4. The PPARD +294 C allele was associated with higher incidence of left ventricular hypertrophy (LVH) in all male patients with body mass index >27. In addition, the CHD patients who were +294 C allele carriers had a 2.48-fold higher risk of LVH than subjects homozygous for the T allele. An increasing effect of the PPARD +294 C allele was shown on serum LDL-C levels in nondiabetic CHD patients. In addition, the results suggested that the +294 C allele might be associated with an increased LVH risk especially in male CHD patients. Furthermore, gene-gene interaction between the PPARD +294T/C and the APOE polymorphisms was observed regarding LDL-C concentrations.
本研究旨在确定载脂蛋白 E(APOE)和过氧化物酶体增殖物激活受体 δ(PPARD)基因多态性变体在冠心病(CHD)发展中的作用,以及土耳其人群中 PPARD 和 APOE 基因-基因相互作用。本研究采用了 223 例 CHD 患者(103 例合并糖尿病,120 例无糖尿病)和 101 例对照的样本。采用聚合酶链反应-限制性片段长度多态性技术检测 PPARD +294T/C 和 APOE 基因型。研究组间 PPARD 和 APOE 基因型分布无差异(p>0.05)。在非糖尿病 CHD 患者中,PPARD +294 C 等位基因的血清低密度脂蛋白胆固醇(LDL-C)水平高于常见的 +294 TT 纯合子基因型(3.83±1.01 vs. 3.33±1.14,p=0.015)。此外,在非糖尿病 CHD 患者中,基于 LDL-C 水平,还检测到 APOE 4 和 PPARD +294 C 等位基因之间存在显著关联(+294 C/APOE4:4.43±0.88 vs. +294 TT/nonAPOE 4:3.48±1.09,p=0.009)。这种关联表明,两种基因对血浆 LDL-C 水平的相互作用按以下顺序增强:+294 T<+294 T-APOE 4<+294 C<APOE 4<+294 C-APOE 4。PPARD +294 C 等位基因与所有 BMI>27 的男性患者左心室肥厚(LVH)发生率升高有关。此外,携带 +294 C 等位基因的 CHD 患者发生 LVH 的风险是 T 等位基因纯合子的 2.48 倍。在非糖尿病 CHD 患者中,PPARD +294 C 等位基因对血清 LDL-C 水平的影响呈递增效应。此外,结果表明,+294 C 等位基因可能与 LVH 风险增加有关,尤其是在男性 CHD 患者中。此外,还观察到 PPARD +294T/C 和 APOE 多态性之间的基因-基因相互作用与 LDL-C 浓度有关。