Ren Huan, Luo Jian-Quan, Ouyang Fan, Cheng Li, Chen Xiao-Ping, Zhou Hong-Hao, Huang Wei-Hua, Zhang Wei
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China.
Front Cardiovasc Med. 2021 Jul 12;8:675222. doi: 10.3389/fcvm.2021.675222. eCollection 2021.
Essential Hypertension (EH) results in the burden of cardiovascular disease (CVD) such as Heart Failure (HF) and Ischemic Stroke (IS). A rapidly emerging field involving the role of Wnt/β-catenin signaling pathway in cardiovascular development and dysfunction has recently drawn extensive attention. In the present study, we conducted a genetic association between genomic variants in Wnt/β-catenin signaling pathway and EH, HF, IS. A total of 95 SNPs in 12 Wnt signaling genes () were genotyped in 1,860 participants (440 patients with EH, 535 patients with HF, 421 patients with IS and 464 normal control subjects) using Sequenom MassArray technology. rs752107(C > T) was strongly associated with an increased risk of EH, HF and IS. Compared with rs752107 CC genotype, the CT genotype carriers had a 48% increased risk of EH (OR = 1.48, 95% CI = 1.12-1.96, = 0.006), the TT genotype conferred a 139% increased risk of EH (OR = 2.39, 95% CI = 1.32-4.34, = 0.003). Regarding HF and IS, the risk of HF in the T allele carriers (CT + TT) was nearly increased by 58% (OR = 1.58, 95% CI = 1.22-2.04, = 4.40 × 10) and the risk of IS was increased by 37% (OR = 1.37, 95% CI = 1.04-1.79, = 0.025). Expression quantitative trait loci (eQTL) analysis indicated that rs752107 C allele corresponded to a significant reduction of expression. We described a genetic variant of rs752107 in Wnt/β-catenin signaling strongly associated with the risk of EH, HF and IS for the first time.
原发性高血压（EH）会导致心血管疾病（CVD）负担，如心力衰竭（HF）和缺血性中风（IS）。一个迅速兴起的领域涉及Wnt/β-连环蛋白信号通路在心血管发育和功能障碍中的作用，最近受到了广泛关注。在本研究中，我们对Wnt/β-连环蛋白信号通路中的基因组变异与EH、HF、IS进行了基因关联研究。使用Sequenom MassArray技术对12个Wnt信号基因中的95个单核苷酸多态性（SNPs）在1860名参与者（440例EH患者、535例HF患者、421例IS患者和464名正常对照受试者）中进行了基因分型。rs752107（C>T）与EH、HF和IS风险增加密切相关。与rs752107 CC基因型相比，CT基因型携带者患EH的风险增加48%（OR = 1.48，95%CI = 1.12 - 1.96，P = 0.006），TT基因型使EH风险增加139%（OR = 2.39，95%CI = 1.32 - 4.34，P = 0.003）。对于HF和IS，T等位基因携带者（CT + TT）患HF的风险增加近58%（OR = 1.58，95%CI = 1.22 - 2.04，P = 4.40×10），患IS的风险增加37%（OR = 1.37，95%CI = 1.04 - 1.79，P = 0.025）。表达数量性状基因座（eQTL）分析表明，rs752107 C等位基因对应于表达的显著降低。我们首次描述了Wnt/β-连环蛋白信号通路中与EH、HF和IS风险密切相关的rs752107基因变异。
