Coincidence of Obesity-Associated Mitochondrial Single Nucleotide Polymorphisms with those Detected in Elite Endurance Runners:

0273 PURPOSE: We hypothesize that certain mitochondrial single nucleotide polymorphisms (mtSNPs) are associated with high efficiency of the mitochondrial oxidative phosphorylation system and that these polymorphisms are associated not only with obesity but also with high performance in endurance running. To examine this hypothesis, we compared the mtSNPs frequently detected in young obese adults with those detected in elite marathon runners. METHODS: We directly sequenced the entire mitochondrial genomes of 96 obese young male adults and 96 non-obese ones to identify obesity-associated mtSNPs. Then, we compared these mtSNPs with those previously detected in elite endurance runners. All subjects gave written consent to the study. RESULTS: We identified 15 obesity-associated mtSNPs in the protein-coding regions of the mitochondrial genome. These mtSNPs were classified into 2 haplogroups, M7b2 and A1a, and were identical with those previously detected in elite marathon runners. The details are as follow: 1) We determined the entire sequence of the mitochondrial genome of a gold medalist of a male marathon race. His mtSNPs included 4048G>A (ND1, Asp248Asn). This mtSNP is one of 9 tightly linked mtSNPs that were detected in 7 of 96 obese males but in only 1 of 96 non-obese males (p = 0.032). These mtSNPs represent haplogroup M7b2. 2) We also identified a mtSNP, 8794C>T, which was associated with high performance in endurance running. We sequenced the mitochondrial ATP synthase subunit 8 gene of 10 elite female runners, and detected this 8794C>T in 5 of 10 runners (ECSS 2003). This mtSNP was also detected in 9 of 96 obese males, whereas it was detected in only 4 of 96 non-obese males. It was also tightly linked with an A insertion at np 2151 of the 16S rRNA gene and with 4 synonymous substitutions. The frequencies of these 5 mtSNPs, representing the haplogroup A1a, were higher in the obese group than in the non-obese group (p = 0.050). CONCLUSIONS: These results suggest that individuals with haplogroups M7b2 and A1a may exhibit extremely high performance in endurance running due to the high capacity of their oxidative phosphorylation system but that, when such individuals with this haplogroup experience sedentary life, they easily become obese because of the high efficiency of their mitochondrial energy conservation system.