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探讨土耳其冠心病患者 PPARD 和 APOE 基因的多态性变异。

Investigation of polymorphic variants of PPARD and APOE genes in Turkish coronary heart disease patients.

机构信息

Department of Molecular Medicine, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.

出版信息

DNA Cell Biol. 2012 May;31(5):867-75. doi: 10.1089/dna.2011.1464. Epub 2012 Jan 25.

DOI:10.1089/dna.2011.1464
PMID:22277050
Abstract

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.

摘要

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。

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