Hypertension in High School Students: Genetic and Environmental Factors The HYGEF Study

Hypertension in High School Students: Genetic and Environmental Factors The HYGEF Study
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DOI:
10.1161/hypertensionaha.119.13818
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发表时间:
2020-01-01
期刊:
影响因子:
8.3
通讯作者:
Manunta, Paolo
Manunta, Paolo
中科院分区:
医学1区
文献类型:
--
作者:
Bigazzi, Roberto;Zagato, Laura;Manunta, Paolo

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年轻人的高血压和肥胖是肾脏和心血管事件的主要危险因素,这些事件可能在成年后发生。在一项队列观察研究中应用了候选基因方法,我们收集了 2638 名高中青少年的数据。参与者接受了人体测量和血压 (BP) 测量,并采集唾液和尿液样本,分别用于基因组 DNA 提取和肾功能评估。我们测试了先前与成人盐敏感性高血压有关的候选基因是否也会影响青少年的血压。由于炎症机制可能与高血压的病理生理学以及活性氧引起的内皮功能障碍和动脉粥样硬化有关,因此对根据 ADD1(α 内收蛋白)rs4961 基因型分层的青少年亚组中炎症和氧化应激标记物的基线尿排泄量进行了评估。对 BP 值与遗传多态性的回归分析,强调了与 LSS(羊毛甾醇合酶,rs2254524)错义变体的关联,LSS 是一种编码参与内源性哇巴因合成的酶的基因。较高的舒张压和收缩压与 LSS A 等位基因相关(分别为 P=0.011 和 P=0.023)。 BP 结果与另外 5 个 SNP 相关。 KL (klotho) rs9536314 错义变异与 24 小时尿 Na+ 排泄相关 (P=0.0083)。尿蛋白测试显示IL1β(白细胞介素1β)和白细胞介素10(P
Hypertension and obesity in the young population are major risk factors for renal and cardiovascular events, which could arise in adulthood. A candidate-gene approach was applied in a cohort observational study, in which we collected data from 2638 high school adolescent students. Participants underwent anthropometric and blood pressure (BP) measurements, as well as saliva and urine sample collection for genomic DNA extraction and renal function evaluation, respectively. We tested whether candidate genes previously implicated in salt-sensitive hypertension in adults impact BP also among adolescents. Since inflammatory mechanisms may be involved in pathophysiology of hypertension and in endothelial dysfunction and atherosclerosis through reactive oxygen species, the baseline urinary excretion of inflammatory and oxidative stress markers in a subgroup of adolescents stratified according to ADD1(alpha adducin) rs4961 genotypes was assessed. Regression analysis of BP values with genetic polymorphisms, highlighted an association with a missense variant of LSS (lanosterol synthase, rs2254524), a gene coding for an enzyme involved in endogenous ouabain synthesis. Higher diastolic and systolic BP were associated with LSS A allele (P=0.011 and P=0.023, respectively). BP resulted associated with 5 more SNPs. The KL (klotho) rs9536314 missense variant was associated with 24 hour urinary Na+ excretion (P=0.0083). Urinary protein tests showed a greater excretion of IL1 beta (interleukin 1 beta) and interleukin 10 (P