Abstract
BackgroundRecent publications have reported contradictory data regarding mitochondrial DNA (mtDNA) variation and its association with body mass index. The aim of the present study was to compare the frequencies of mtDNA haplogroups as well as control region (CR) polymorphisms of obese juveniles (n = 248) and obese adults (n = 1003) versus normal weight controls (njuvenile = 266, nadults = 595) in a well-defined, ethnically homogenous, age-matched comparative cohort of Austrian Caucasians.Methodology and Principal FindingsUsing SNP analysis and DNA sequencing, we identified the nine major European mitochondrial haplogroups and CR polymorphisms. Of these, only the T haplogroup frequency was increased in the juvenile obese cohort versus the control subjects [11.7% in obese vs. 6.4% in controls], although statistical significance was lost after adjustment for sex and age. Similar data were observed in a local adult cohort, in which haplogroup T was found at a significantly higher frequency in the overweight and obese subjects than in the normal weight group [9.7% vs. 6.2%, p = 0.012, adjusted for sex and age]. When all obese subjects were considered together, the difference in the frequency of haplogroup T was even more clearly seen [10.1% vs. 6.3%, p = 0.002, OR (95% CI) 1.71 (1.2–2.4), adjusted for sex and age]. The frequencies of the T haplogroup-linked CR polymorphisms C16294T and the C16296T were found to be elevated in both the juvenile and the adult obese cohort compared to the controls. Nevertheless, no mtDNA haplogroup or CR polymorphism was robustly associated with any of several investigated metabolic and cardiovascular parameters (e.g., blood pressure, blood glucose concentration, triglycerides, cholesterol) in all obese subjects.Conclusions and SignificanceBy investigation of this large ethnically and geographically homogenous cohort of Middle European Caucasians, only mtDNA haplogroup T was identified as an obesity risk factor.
Highlights
The heritability of obesity has long been appreciated
By investigation of this large ethnically and geographically homogenous cohort of Middle European Caucasians, only mitochondrial DNA (mtDNA) haplogroup T was identified as an obesity risk factor
A Finnish study of identical twins who were either concordant or discordant for obesity showed that, independent of genetic factors, obesity was associated with poor fitness, low insulin sensitivity, and decreased transcript levels of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) pathways [5]
Summary
Studies focused on monogenic and syndromal forms of extreme obesity, while subsequent genome-wide association studies (GWAS) of common genetic variants have identified novel loci. A study of children with a suspected disorder of oxidative phosphorylation (OXPHOS) found a significant correlation between mitochondrial energy production and age-related body mass index (BMI) [4]. A few studies have used large population samples to test the hypothesis that genetic variants in mtDNA might contribute to susceptibility to obesity, but they yielded conflicting results [6,7,8,9] (Table 1). Recent publications have reported contradictory data regarding mitochondrial DNA (mtDNA) variation and its association with body mass index.
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