Agosti Pasquale, Mancini Ilaria, Sadeghian Saeed, Pagliari Maria Teresa, Abbasi Seyed Hesameddin, Pourhosseini Hamidreza, Boroumand Mohammadali, Lotfi-Tokaldany Masoumeh, Pappalardo Emanuela, Maino Alberto, Rosendaal Frits R, Peyvandi Flora
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, and Fondazione Luigi Villa, Milan, Italy.
Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Res Pract Thromb Haemost. 2023 Jan 11;7(1):100048. doi: 10.1016/j.rpth.2023.100048. eCollection 2023 Jan.
Factor V Leiden (FVL) and factor II c.∗97G>A (rs1799963) are genetic risk factors for venous thromboembolism. Their contribution to coronary artery disease (CAD) is less clear.
This study aimed to investigate the association between FVL, rs1799963, and premature CAD in Iranians.
We performed a genetic case-control study of 944 cases and 1081 controls from the premature CAD Milano-Iran study, including patients aged 18-55 (female) and 18-45 years (male) who underwent coronary angiography at the Tehran Heart Centre (Iran) in 2004-2011. Cases had luminal stenosis ≥50% in at least 1 main coronary artery or branch. Controls were age- and sex-matched with no CAD history. FVL and rs1799963 were genotyped using TaqMan SNP genotyping assays. Association was tested by logistic regression adjusted for matching factors and ethnicity. Effect modification by sex and cardiovascular risk factors (metabolic [obesity, hypertension, hyperlipidemia, and diabetes], and smoking) was assessed.
The risk of premature CAD was increased by 50% in FVL carriers (adjusted odds ratio [adjOR] 1.54 [95% CI, 0.95-2.48]) and slightly reduced in rs1799963 carriers (adjOR 0.71 [95% CI, 0.40-1.27]). These effects were more pronounced in women than men (FVL, adjOR 1.66 vs 1.25; rs1799963, adjOR 0.60 vs 1.07). The risk of premature CAD was substantially increased in carriers of FVL with at least 1 metabolic risk factor compared with noncarriers without metabolic risk factors (adjOR 25.14 [95% CI, 12.51-50.52]).
FVL but not FII rs1799963 was associated with an increased risk of CAD in young Iranians. This risk increased considerably when combined with metabolic cardiovascular risk factors.
凝血因子V莱顿突变（FVL）和凝血因子II c.∗97G>A（rs1799963）是静脉血栓栓塞的遗传风险因素。它们对冠状动脉疾病（CAD）的影响尚不清楚。
本研究旨在调查伊朗人群中FVL、rs1799963与早发CAD之间的关联。
我们对来自早发CAD米兰-伊朗研究的944例病例和1081例对照进行了基因病例对照研究，包括2004年至2011年在德黑兰心脏中心（伊朗）接受冠状动脉造影的18至55岁（女性）和18至45岁（男性）患者。病例至少有1条主要冠状动脉或分支的管腔狭窄≥50%。对照与病例年龄和性别匹配且无CAD病史。使用TaqMan SNP基因分型检测对FVL和rs1799963进行基因分型。通过对匹配因素和种族进行校正的逻辑回归检验关联。评估性别和心血管危险因素（代谢性[肥胖、高血压、高脂血症和糖尿病]以及吸烟）的效应修正。
FVL携带者早发CAD的风险增加50%（校正比值比[adjOR] 1.54 [95%置信区间，0.95 - 2.48]），而rs1799963携带者的风险略有降低（adjOR 0.71 [95%置信区间，0.40 - 1.27]）。这些效应在女性中比男性更明显（FVL，adjOR 1.66对1.25；rs1799963，adjOR 0.60对1.07）。与没有代谢危险因素的非携带者相比，至少有1种代谢危险因素的FVL携带者早发CAD的风险大幅增加（adjOR 25.14 [95%置信区间，12.51 - 50.52]）。
在年轻的伊朗人中FVL而非FII rs1799963与CAD风险增加相关。当与代谢性心血管危险因素合并时，这种风险显著增加。
