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Variation in mitochondrial genes in obesity ; Variation mitochondrialer Gene bei Adipositas
In 2008, more than 35 % of the world’s adult population were overweight (BMI ≥ 25 kg/m^2) and 11 % were obese (BMI ≥ 30 kg/m^2). Although in the last five to ten years a stabilizing trend in prevalence had been observed, obesity still is a major global health problem, because of health consequences in later life such as type 2 diabetes mellitus (T2DM). Both environmental and genetic factors were shown to contribute to the global obesity epidemic. In empirical studies, the heritability of the BMI variance was estimated to 40 % to 70 %. Interestingly, larger correlations in BMI between mothers and their offspring than between fathers and their offspring were found. Mitochondria are well known as cellular power plants and contain an exclusively maternally inherited circular DNA (mtDNA) of 16,569 bp with 37 genes of which 13 are protein coding subunits of the oxidative phosphorylation system (OXPHOS). On the other hand, ~1,000 to 1,500 nuclear-encoded genes are required to maintain mitochondrial biogenesis. Alterations in mitochondrial function were found in obese individuals. Both variation of mtDNA and nuclear-encoded mitochondrial genes have been analyzed in association with obesity within the present PhD thesis, because of (1) the central role of mitochondria in the energy metabolism, (2) hints of altered mitochondrial function in obese individuals, and (3) the parental effect of correlations in BMI to which genetic variation in the exclusively maternally inherited mtDNA might contribute. For analysis of variation in mtDNA, first of all, an association study of up to 40 array-based SNPs of mtDNA (all but one of the SNPs located in mtDNA coding region) was performed in a case-control (CC) sample of 1,158 (extremely) obese cases and 435 lean adult controls (discovery). SNPs were analyzed as single SNPs and as haplogroups determined by HaploGrep. Analysis was done (a) in all individuals and (b) stratified by gender. For independent confirmation, nominally associated SNPs were followed-up among adults of three ...
Variation in mitochondrial genes in obesity ; Variation mitochondrialer Gene bei Adipositas
In 2008, more than 35 % of the world’s adult population were overweight (BMI ≥ 25 kg/m^2) and 11 % were obese (BMI ≥ 30 kg/m^2). Although in the last five to ten years a stabilizing trend in prevalence had been observed, obesity still is a major global health problem, because of health consequences in later life such as type 2 diabetes mellitus (T2DM). Both environmental and genetic factors were shown to contribute to the global obesity epidemic. In empirical studies, the heritability of the BMI variance was estimated to 40 % to 70 %. Interestingly, larger correlations in BMI between mothers and their offspring than between fathers and their offspring were found. Mitochondria are well known as cellular power plants and contain an exclusively maternally inherited circular DNA (mtDNA) of 16,569 bp with 37 genes of which 13 are protein coding subunits of the oxidative phosphorylation system (OXPHOS). On the other hand, ~1,000 to 1,500 nuclear-encoded genes are required to maintain mitochondrial biogenesis. Alterations in mitochondrial function were found in obese individuals. Both variation of mtDNA and nuclear-encoded mitochondrial genes have been analyzed in association with obesity within the present PhD thesis, because of (1) the central role of mitochondria in the energy metabolism, (2) hints of altered mitochondrial function in obese individuals, and (3) the parental effect of correlations in BMI to which genetic variation in the exclusively maternally inherited mtDNA might contribute. For analysis of variation in mtDNA, first of all, an association study of up to 40 array-based SNPs of mtDNA (all but one of the SNPs located in mtDNA coding region) was performed in a case-control (CC) sample of 1,158 (extremely) obese cases and 435 lean adult controls (discovery). SNPs were analyzed as single SNPs and as haplogroups determined by HaploGrep. Analysis was done (a) in all individuals and (b) stratified by gender. For independent confirmation, nominally associated SNPs were followed-up among adults of three ...
Variation in mitochondrial genes in obesity ; Variation mitochondrialer Gene bei Adipositas
Knoll, Nadja (author) / Hinney, Anke
2013-12-17
Theses
Electronic Resource
English
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