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Study of genetic and infectious risk factors in the pathogenesis of obesity in Czech adolescents.
Dušátková, Lenka ; Zamrazilová, Hana (advisor) ; Zapletalová, Jiřina (referee) ; Müllerová, Dana (referee)
4 Abstract The prevalence of obesity and its related cardiometabolic complications in children remains high across the world. Obesity is a multifactorial disease caused by interaction between genes and environmental factors. Genome-wide association studies have discovered several single nucleotide polymorphisms associated with obesity. A causal role of infection in the pathogenesis of obesity has also been considered, particularly the role of adenovirus 36 (Adv36). The aim of the Ph.D. thesis was to investigate the associations of obesity susceptibility loci (TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, FTO) and Adv36 infection with obesity-related characteristics and complications in the Czech adolescent population. The results are described in eight publications, of which six are original papers and two are reviews. Studies were performed on a cohort of Czech adolescents recruited either from the general population (1,533 individuals from the epidemiological study) and from in-patient or outpatient weight management clinics (562 overweight/obese individuals underwent an intervention). The results demonstrated an association of TMEM18, SEC16B and FTO gene variants with obesity. Some variants of the genes involved in hypothalamic regulation of energy homeostasis − MC4R, BDNF, PCSK1 − were related to...
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Study of candidate genes for obesity in children and adolescents.
Dušátková, Lenka ; Zamrazilová, Hana (advisor) ; Vaňková, Markéta (referee)
Obesity is one of the most common metabolic diseases in the whole world that increases risk of many other health problems. Origin of this multifactorial disease is influenced by many factors, including genetic ones. This work was realized within the project COPAT (Childhood Obesity Prevalence And Treatment). The main goal was to study two single nucleotide polymorphisms (SNPs) (rs9939609, rs1421085) in FTO (fat mass and obesity associated) gene and their possible impact on anthropometric traits, body composition or weight reduction. We examined two groups - 356 overweight and obese children who took part in 4-weeks weight reduction program and 412 Czech adolescents of the control group. Genotyping was performed using TaqMan allelic discrimination. Weight reduction program resulted in significantly loss of most of the examinated antropometric traits including body fat mass and visceral fat (p < 0,001). Results showed significant association of the minor A-alelle of rs9939609 with overweight and obesity (OR = 1,33; 95%CI 1,08−1,64) as well as of the minor C-alelle of rs1421085 (OR = 1,38; 95%CI 1,12−1,70). Nevertheless, there was no clear evidence of interaction between the FTO rs9939609 genotype and antropometric traits, body composition or weight loss. Results of this work confirmed that tested...
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