Genetic polimorphisms associated to obesity and cardiovascular disease risk factors in European adolescents

Abstract

Cardiovascular diseases (CVDs) are the main cause of premature death and chronic disability worldwide. CVD events occur most frequently during or after the fifth decade of life; however, there is evidence indicating that the precursors of CVD have its origin in the first decades of life. Therefore, prevention is fundamental to reduce the incidence of these pathologies, especially in young people. CVDs are a result of complex interactions between environmental and genetic risk factors. The overall aim of the present Doctoral Thesis was to study the genetic variants of Uncoupling proteins (UCP), cilliary neurotrophic factor (CNTF), lipoprotein lipase (LPL) and adiponectin (ADIPOQ) genes associated with obesity and other CVD risk factors in adolescents and the potential interaction with physical activity (PA). We observed significant associations of several single nucleotide polymorphisms (SNPs) of CNTF and UCPs with adiposity markers such as body mass index (BMI), waist circumference, waist to height ratio or waist to hip ratio in European adolescents. Moreover, we also observed an interaction between PA and the UCP1rs2071415 polymorphism on waist to hip ratio. Also, other main findings were the significant association of SNPs of LPL, UCP and ADIPOQ with several CVD risk factors such as serum markers, blood pressure or risk score. We also observed that LPL alleles of rs1534649 and rs258 related to higher values of adiposity markers tend to be associated with less adiposity under high levels of PA. Finally, we have used an in silico technique to search new potential novel candidate genes of physiology of brown adipose tissue (BAT) using UCP1 as core gene. In summary, findings of the present doctoral thesis provide more insights into the genetic role in the predisposition to develop a CVD in European adolescents. These findings also provide information about the potential effect of PA on the attenuation of some of the associations observed between genotypes and CVD phenotypes. Finally, we show a list with 102 novel candidate genes, which set up the BAT-connectome. These potential novel genes suggested new research future lines to improve the knowledge of genetic architecture of BAT.