Lumpuy-Castillo Jairo, Vales-Villamarín Claudia, Mahíllo-Fernández Ignacio, Pérez-Nadador Iris, Soriano-Guillén Leandro, Lorenzo Oscar, Garcés Carmen
Laboratory of Diabetes and Vascular Pathology, IIS-Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Spanish Biomedical Research Centre on Diabetes and Associated Metabolic Disorders (CIBERDEM) Network, Madrid, Spain.
Front Cardiovasc Med. 2022 May 2;9:888830. doi: 10.3389/fcvm.2022.888830. eCollection 2022.
In the cardiovascular (CV) system, overactivation of the angiotensin converting enzyme (ACE) may trigger deleterious responses derived from angiotensin (Ang)-II, which can be attenuated by stimulation of ACE2 and subsequent Ang-(1-7) metabolite. However, exhibits a high degree of genetic polymorphism that may affect its structure and stability, interfering with these cardioprotective actions. The aim of this study was to analyse the relationship of polymorphisms with cardiovascular risk factors in children.
Five -single nucleotide polymorphisms (SNP), rs4646188, rs2158083, rs233575, rs879922, and rs2074192, previously related to CV risk factors, were analyzed in a representative sample of 12-16-year-old children and tested for their potential association with anthropometric parameters, insulin levels and the lipid profile.
Girls ( = 461) exhibited lower rates of overweight, obesity, blood pressure, and glycemia than boys ( = 412), though increased plasma lipids. The triglycerides (TG)/HDL-C ratio was, however, lower in females. Interestingly, only in girls, the occurrence of overweight/obesity was associated with the SNPs rs879922 [OR 1.67 (1.02-2.75)], rs233575 [OR 1.98 (1.21- 3.22)] and rs2158083 [OR 1.67 (1.04-2.68)]. Also, TG levels were linked to the rs879922, rs233575, and rs2158083 SNPs, and the TG/HDL-C ratio was associated with rs879922 and rs233575. Levels of TC and LDL-C were associated with rs2074192 and rs2158083. Furthermore, the established cut-off level for TG ≥ 90 mg/dL was related to rs879922 [OR 1.78 (1.06-2.96)], rs2158083 [OR 1.75 (1.08-2.82)], and rs233575 [OR 1.62 (1.00-2.61)]. The cut-off level for TC ≥ 170 mg/dL was associated with rs2074192 OR 1.54 (1.04-2.28) and rs2158083 [OR 1.53 (1.04-2.25)]. Additionally, the haplotype (C-G-C) derived from rs879922-rs2158083-rs233575 was related to higher prevalence of overweight/obesity and TG elevation.
The expression and activity of ACE2 may be essential for CV homeostasis. Interestingly, the -SNPs rs879922, rs233575, rs2158083 and rs2074192, and the haplotype (C-G-C) of the three former could induce vulnerability to obesity and hyperlipidemia in women. Thus, these SNPs might be used as predictive biomarkers for CV diseases and as molecular targets for CV therapy.
在心血管（CV）系统中，血管紧张素转换酶（ACE）的过度激活可能引发源自血管紧张素（Ang）-II的有害反应，而刺激ACE2及随后的Ang-（1-7）代谢产物可减弱这种反应。然而，ACE2表现出高度的基因多态性，这可能影响其结构和稳定性，干扰这些心脏保护作用。本研究的目的是分析ACE2基因多态性与儿童心血管危险因素之间的关系。
在12至16岁儿童的代表性样本中分析了五个先前与心血管危险因素相关的单核苷酸多态性（SNP），即rs4646188、rs2158083、rs233575、rs879922和rs2074192，并测试它们与人体测量参数、胰岛素水平和血脂谱的潜在关联。
女孩（n = 461）的超重、肥胖、血压和血糖发生率低于男孩（n = 412），不过血浆脂质有所增加。然而，女性的甘油三酯（TG）/高密度脂蛋白胆固醇（HDL-C）比值较低。有趣的是，仅在女孩中，超重/肥胖的发生与SNP rs879922 [比值比（OR）1.67（1.02 - 2.75）]、rs233575 [OR 1.98（1.21 - 3.22）]和rs2158083 [OR 1.67（1.04 - 2.68）]相关。此外，TG水平与rs879922、rs233575和rs2158083这几个SNP有关，TG/HDL-C比值与rs879922和rs233575相关。总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平与rs2074192和rs2158083相关。此外，设定的TG≥90mg/dL的临界值与rs879922 [OR 1.78（1.06 - 2.96）]、rs2158083 [OR 1.75（1.08 - 2.82）]和rs233575 [OR 1.62（1.00 - 2.61）]相关。TC≥170mg/dL的临界值与rs2074192的OR为1.54（1.04 - 2.28）以及rs2158083 [OR 1.53（1.04 - 2.25）]相关。此外，源自rs879922 - rs2158083 - rs233575 的单倍型（C - G - C）与超重/肥胖和TG升高的较高患病率相关。
ACE2的表达和活性可能对心血管稳态至关重要。有趣的是，ACE2 - SNPs rs879922、rs233575、rs2158083和rs2074192，以及前三个的单倍型（C - G - C）可能使女性易患肥胖和高脂血症。因此，这些SNP可作为心血管疾病的预测生物标志物以及心血管治疗的分子靶点。
