Liang Xiuwen, He Tingting, Gao Lihong, Wei Libo, Rong Di, Zhang Yu, Liu Yu
Cardiology Department, Hulunbeir China Mongolia Hospital Affiliated to the Teaching Hospital of Inner Mongolia Medical University, No. 58 West Street, Hailar District, Hulunbuir, Inner Mongolia 021000, China.
Cardiology Department, Hulunbeir People's Hospital, No. 20, Shengli Street, Hailar District, Hulunbuir, Inner Mongolia 021008, China.
PPAR Res. 2022 Mar 20;2022:2054876. doi: 10.1155/2022/2054876. eCollection 2022.
Both rs1801133 mutation on Methylenetetrahydrofolate reductase (MTHFR) gene and transcription factor peroxisome proliferator-activated gamma (PPARG) have been associated with plasma homocysteine (Hcy) levels and hypertension. However, their role in H-type hypertension remains unclear. In this study, we first tested the association between rs1801133 genotypes and Hcy level in H-type hypertension using clinical profiles collected from 203 patients before and after the treatment using enalapril maleate and folic acid tablets (EMFAT). Then, we constructed a literature-based pathway analysis to explore the role of the rs1801133-PPARG signaling pathway in H-type hypertension and its treatment. Although presented similar blood pressure, the patients with TT genotype of rs1801133 were much younger ( value <0.05) and significantly higher in Hcy levels ( = 6.11 and < 0.005) than that in the CC and CT genotype groups. Pathway analysis showed that T-allele of rs1801133 could inhibit the expression of PPARG through the downregulation of folate levels and upregulation of Hcy levels, which increased the risk of hypertension and hyperhomocysteinemia. Treatment using EMFAT led to similarly decreased Hcy levels for all patients with different genotypes ( = 86.00; < 0.36), which may occur partially through the activation of PPARG. Moreover, even after treatment, the patients with TT genotype still presented significantly higher Hcy levels ( = 7.87 and < 0.001). Our results supported that rs1801133 mutation could play a role in H-type hypertension, which might be partially through the downregulation of PPARG. Moreover, PPARG might also be involved in treating H-type hypertension using EMFAT.
亚甲基四氢叶酸还原酶（MTHFR）基因上的rs1801133突变和转录因子过氧化物酶体增殖物激活受体γ（PPARG）均与血浆同型半胱氨酸（Hcy）水平及高血压有关。然而，它们在H型高血压中的作用仍不明确。在本研究中，我们首先利用从203例使用马来酸依那普利叶酸片（EMFAT）治疗前后的患者收集的临床资料，检测了H型高血压患者中rs1801133基因型与Hcy水平之间的关联。然后，我们构建了基于文献的通路分析，以探究rs1801133-PPARG信号通路在H型高血压及其治疗中的作用。尽管rs1801133的TT基因型患者与CC和CT基因型组患者的血压相似，但TT基因型患者更年轻（P值<0.05），且Hcy水平显著更高（P = 6.11，P<0.005）。通路分析表明，rs1801133的T等位基因可通过降低叶酸水平和升高Hcy水平来抑制PPARG的表达，从而增加高血压和高同型半胱氨酸血症的风险。使用EMFAT治疗导致不同基因型的所有患者的Hcy水平均有相似程度的降低（P = 86.00；P<0.36），这可能部分是通过激活PPARG实现的。此外，即使在治疗后，TT基因型患者的Hcy水平仍显著更高（P = 7.87，P<0.001）。我们的结果支持rs1801133突变可能在H型高血压中起作用，这可能部分是通过下调PPARG实现的。此外，PPARG可能也参与了使用EMFAT治疗H型高血压的过程。
