Yalım Zafer, Tutgun Onrat Serap, Alan Sümeyra, Aldemir Mustafa, Avşar Alaettin, Doğan İsmet, Onrat Ersel
Department of Cardiology, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey.
Department of Medical Genetics, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey.
Turk Kardiyol Dern Ars. 2020 Jul;48(5):484-493. doi: 10.5543/tkda.2020.15686.
Peripheral artery disease (PAD) is a condition caused by the narrowing of limb arteries due to atherosclerosis. In recent years, polymorphisms in a number of genes have been shown to contribute to the risk of PAD development. However, whether the contribution of these inheritable factors is independent of traditional cardiovascular risk factors remains unclear. This study was an investigation of the effects of diabetes mellitus (DM) and genetic background, examined singly and together, on the pathogenesis of PAD.
The effects of the factor V Leiden (G1691A), factor V H1299R, prothrombin G20210A, factor XIII V34L, B-fibrinogen -455 G>A, PAI-1 4G/5G, HPA1, MTHFR C677T, MTHFR A1298C, ACE I/D, APO B R3500Q, and APOE polymorphisms were evaluated using a cardiovascular disease strip assay (CVD StripAssay). Two groups were created: 100 patients with PAD (50 with DM, 50 without DM) and 60 controls without PAD (30 with DM, 30 without DM).
There was a significantly greater presence of the MTHFR A1298C and PAI 4G/5G homozygous polymorphisms in the PAD patients compared with the control group (p=0.035, p=0.004, respectively). There were no significant associations between the other genotypes and polymorphism frequencies. In the presence of DM, the PAI-1 4G/5G homozygous polymorphism was linked to the formation of PAD (p=0.021). Regression analysis indicated that the PAI-1 4G/5G gene homozygous polymorphism demonstrated a 17.1 times greater risk for DM with PAD [95% confidence interval (CI): 2.113-138.660; p=0.008] and the MTHFR A1298C homozygous polymorphism demonstrated a 316.6 times greater risk (95% CI: 10.763-9315.342; p<0.001) for the possibility of DM with PAD.
The MTHFR A1298C and PAI 4G/5G homozygous polymorphisms may be associated with the development of PAD. The presence of the PAI 4G/5G homozygous polymorphism with DM was a powerful predictor for the development of PAD.
外周动脉疾病（PAD）是一种因动脉粥样硬化导致肢体动脉狭窄引起的病症。近年来，多项研究表明一些基因的多态性会增加患PAD的风险。然而，这些遗传因素的影响是否独立于传统心血管危险因素尚不清楚。本研究旨在探讨糖尿病（DM）和遗传背景单独及共同作用对PAD发病机制的影响。
采用心血管疾病检测条法（CVD StripAssay）评估凝血因子V Leiden（G1691A）、凝血因子V H1299R、凝血酶原G20210A、凝血因子XIII V34L、B - 纤维蛋白原 - 455 G>A、纤溶酶原激活物抑制剂 - 1（PAI - 1）4G/5G、血小板血型抗原1（HPA1）、亚甲基四氢叶酸还原酶（MTHFR）C677T、MTHFR A1298C、血管紧张素转换酶（ACE）I/D、载脂蛋白B R3500Q和载脂蛋白E（APOE）基因多态性。研究分为两组：100例PAD患者（50例合并DM，50例不合并DM）和60例无PAD的对照者（30例合并DM，30例不合并DM）。
与对照组相比，PAD患者中MTHFR A1298C和PAI 4G/5G纯合多态性的出现频率显著更高（分别为p = 0.035，p = 0.004）。其他基因型与多态性频率之间无显著关联。在合并DM的情况下，PAI - 1 4G/5G纯合多态性与PAD的形成有关（p = 0.021）。回归分析表明，PAI - 1 4G/5G基因纯合多态性使合并DM的PAD发病风险增加17.1倍[95%置信区间（CI）：2.113 - 138.660；p = 0.008]，而MTHFR A1298C纯合多态性使合并DM的PAD发病风险增加316.6倍（95% CI：10.763 - 9315.342；p < 0.001）。
MTHFR A1298C和PAI 4G/5G纯合多态性可能与PAD的发生有关。PAI 4G/5G纯合多态性合并DM是PAD发生的有力预测指标。
