Polymorphisms in the Control Region of Mitochondrial DNA Associate with Elite Japanese Athlete Status

Mitochondrial haplogroups G1 and F derived from the analysis of haplogroup-specific polymorphisms in the control region (hypervariable sequence I) of mitochondrial DNA (mtDNA) were found to associate with elite Japanese athlete status (Mikami et al, Br J Sports Med, 2010 [Epub ahead of print]). The mitochondrial DNA control region contains various non-haplogroup-specific polymorphisms that have previously been found to associate with trainability in VO2max, metabolic syndrome and type 2 diabetes mellitus; all closely related to mitochondrial function. PURPOSE: To identify the polymorphisms in the control region of mtDNA that may significantly association with elite Japanese athlete status. METHODS: Subjects comprised 185 elite Japanese athletes who had represented Japan at international competitions (i.e. 100 endurance/middle-power athletes: EMA; 85 sprint/power athletes: SPA) and 672 Japanese controls (CON) (http://mtsnp.tmig.or.jp/mtsnp/index.shtml). The mtDNA control region (m.16024-576) was analyzed by direct sequencing and polymorphisms were identified by comparison with the revised Cambridge Reference Sequence. Frequency differences of polymorphisms between athletes and controls were examined by Chi-square tests. RESULTS: When the frequencies of common polymorphisms (minor allele frequency >1%) in the mtDNA control region were compared between athletes and controls, the frequencies of 4 polymorphisms were significantly different between EMA and CON (m.16140T>C, m.152T>C, m.514delCA and poly-C stretch at m.568-573) and another 4 polymorphisms between SPA and CON (m.16278C>T, m.151C>T, m.203G>A and m.204T>C). Two of these polymorphisms, namely m.151C>T (EMA-related polymorphism) and m.152T>C (SPA-related polymorphism), are located near the second heavy-strand replication origin, and m.151C>T has been associated with increased mtDNA content in patients with type 2 diabetes mellitus. CONCLUSIONS: These findings suggest that several polymorphisms detected in the control region of mtDNA may influence physical performance due to changes in transcription and replication of mtDNA.