Department of Emergency and Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (mainland).
Department of Hypertension Research, Beijing Anzhen Hospital, Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China (mainland).
Med Sci Monit. 2019 Apr 3;25:2419-2428. doi: 10.12659/MSM.915272.
BACKGROUND Many studies have shown that hypertension may contribute to thoracic aortic dissection (TAD). Among the factors that modulate hypertension are endoplasmic reticulum stress and vascular smooth muscle cell proliferation which are in turn modulated by mitofusion-2 (Mfn2). Specifically, we determined, in the Han Chinese population, whether single nucleotide polymorphisms (SNPs) of Mfn2 influenced the occurrence of TAD. MATERIAL AND METHODS Six tagging SNPs of Mfn2 (rs2236057, rs3766741, rs2236058, rs17037564, rs2295281, and rs2336384) were genotyped using a TaqMan assay in 200 TAD patients and 451 health individuals from the Han Chinese population. RESULTS Logistic regression analysis indicated CC genotype of rs2295281 was highly linked to an increased risk of TAD (TT+CT versus CC, OR=0.540, 95% CI [0.320-0.911], P=0.021), implying that TT genotype and CT genotype of rs2295281 have a lower risk for TAD. Logistic regression analysis also indicated that rs2236058 was highly linked to the risk of TAD based on recessive genetic model, which indicated that the GG genotype was a protective factor against TAD (GG versus (CG+CC), OR=0.545, 95% CI [0.351-0.845], P=0.007). CG genotype and CC genotype of rs2236058 had a higher risk for TAD. In addition, rs2236058 was linked to the risk of TAD in the recessive genetic and homozygous models in the normotensive subgroup (GG versus (CG+CC), OR=0.298, 95% CI [0.112-0.792], P=0.015; GG versus CC, OR=0.528, 95% CI [0.302-0.925], P=0.026) but not in the hypertension subgroup. CONCLUSIONS Our findings showed that the occurrence of TAD in a Han Chinese population was influenced by Mfn2 polymorphisms.
许多研究表明，高血压可能导致胸主动脉夹层（TAD）。调节高血压的因素包括内质网应激和血管平滑肌细胞增殖，而这些又受线粒体融合蛋白 2（Mfn2）调节。具体而言，我们在汉族人群中确定了 Mfn2 的单核苷酸多态性（SNP）是否影响 TAD 的发生。
使用 TaqMan 检测法，在 200 名 TAD 患者和 451 名汉族健康个体中对 Mfn2 的 6 个标记 SNP（rs2236057、rs3766741、rs2236058、rs17037564、rs2295281 和 rs2336384）进行了基因分型。
Logistic 回归分析表明，rs2295281 的 CC 基因型与 TAD 风险增加高度相关（TT+CT 与 CC，OR=0.540，95%CI[0.320-0.911]，P=0.021），这意味着 rs2295281 的 TT 基因型和 CT 基因型患 TAD 的风险较低。Logistic 回归分析还表明，rs2236058 基于隐性遗传模型与 TAD 风险高度相关，这表明 GG 基因型是 TAD 的保护因素（GG 与（CG+CC），OR=0.545，95%CI[0.351-0.845]，P=0.007）。rs2236058 的 CG 基因型和 CC 基因型患 TAD 的风险较高。此外，rs2236058 与正常血压亚组的隐性遗传和纯合模型中的 TAD 风险相关（GG 与（CG+CC），OR=0.298，95%CI[0.112-0.792]，P=0.015；GG 与 CC，OR=0.528，95%CI[0.302-0.925]，P=0.026），但在高血压亚组中则不然。
我们的研究结果表明，汉族人群 TAD 的发生受 Mfn2 多态性影响。
