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

Abstract

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 IL1β (interleukin 1β) and interleukin 10 (P<0.0001) in carriers of the ADD1 rs4961 T allele. In conclusion, 3 missense gene variants already implicated in adult hypertension impact BP or Na+ excretion among adolescents, and, together with activated pro-inflammatory pathways, might predispose to early cardiovascular damage.

• Authors: Roberto Bigazzi, Laura Zagato, Chiara Lanzani, Simone Fontana, Elisabetta Messaggio, Simona Delli Carpini, Lorena Citterio, Marco Simonini, Elena Brioni, Cristiano Magnaghi, Gualtiero Ivanoe Colombo, Giada Santini, Francesca Nistri, Filippo Cellai, Salvatore Lenti, Stefano Bianchi, Giovanni Battista Pertosa, Maria Teresa Rocchetti, Massimo Papale, Valeria Mezzolla, Loreto Gesualdo, Maria Pina Concas, Vito Campese, Paolo Manunta
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 75 Issue 1 Pg. 71-78 (01 2020) ISSN: 1524-4563 [Electronic] United States
• PMID: 31760884 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adolescent
• Alleles
• Blood Pressure (genetics)
• Female
• Gene-Environment Interaction
• Genetic Predisposition to Disease
• Genotype
• Humans
• Hypertension (etiology, genetics)
• Male
• Polymorphism, Single Nucleotide