A candidate-gene based approach for assessing genetic predisposition to childhood obesity

Lagou, Vasiliki (2007) A candidate-gene based approach for assessing genetic predisposition to childhood obesity. PhD thesis, University of Glasgow.

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Abstract

The main aim of the present series of experiments was to assess the influence of selected candidate genes on several adiposity-related phenotypes in a large cohort of toddlers and preschoolers from Greece using both genotype- and haplotype-based approaches. Investigating the impact of genetic polymorphisms on adiposity in the young may reveal stronger associations than in older ages since the environment has had less time to take effect. Anthropometric measurements and buccal cell samples, from where genomic DNA was extracted, were obtained from 2374 children aged 1-6 years, all in public and private nurseries in Greece. The aim of the first experiment (Chapter 3) was to assess developmental changes in adiposity in the present population of Greek toddlers and preschoolers. This was achieved by determining the prevalence of overweight and obesity in this population using specific BMI cut-off points based on UK and US national reference data. The aim of the second experiment (Chapter 4) was to assess the potential influences of ACE I/D polymorphism and its interaction with age and/or gender on adiposity-related phenotypes in the cohort of Greek toddlers and preschoolers. A significant main effect of the ACE I/D polymorphism on BMI and significant interactions between I/D genotype and age for the same phenotype were revealed. The aim of the third experiment (Chapter 5) was to investigate the potential influence of five genetic polymorphisms in ADRB genes on adiposity-related phenotypes in the Greek children and their potential interactions with age and/or gender. Significant main effects of ADRB2 C16 on waist and hip circumferences and significant interactions between Cl6 genotypes and age for the same phenotypes were revealed. The aim of the fourth and final experiment (Chapter 6) was to assess the influence of two polymorphisms in PPAR? gene on adiposity-related phenotypes in the Greek toddlers and preschoolers. Genetic analysis based on Prol2Ala genotypes revealed that the rare Alal2 and T1431 alleles had no significant main effect on adiposity-related phenotypes. Interactions with age and/or gender were either not significant. A synergistic effect of PPAR? Pro 12Ala and ADRB3 Arg64Trp polymorphisms, as well as a modulating effect of BMI on the establishment of associations previously observed in adults was not confirmed in this study. Haplotype-based analysis including both PPAR? polymorphisms revealed no stronger associations of PPAR? diplotypes with adiposity-related indices compared to individual genotypes. Variation in the PPAR? seems not to contribute significantly to the high prevalence of early-onset obesity possibly due to differences in the dietary composition between children and adults. The findings from the genetic analyses suggested that allelic variations in candidate genes simply predispose to the obesity phenotype. With well-conducted genetic studies and with thorough examination of the information with respect to genetic associations, progress in understanding and management of obesity can be foreseen. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Yannis Pitsiladis
Keywords: Genetics
Date of Award: 2007
Depositing User: Enlighten Team
Unique ID: glathesis:2007-70982
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 09 May 2019 14:28
Last Modified: 09 May 2019 14:28
URI: http://theses.gla.ac.uk/id/eprint/70982

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