Comprehensive analysis of common and rare mitochondrial DNA variants in elite Japanese athletes: a case–control study

Abstract

The purpose of the present study was to identify mitochondrial DNA (mtDNA) polymorphisms and rare variants that associate with elite Japanese athletic status. Subjects comprised 185 elite Japanese athletes who had represented Japan at international competitions (that is, 100 endurance/middle-power athletes: EMA; 85 sprint/power athletes: SPA) and 672 Japanese controls (CON). The entire mtDNA sequences (16 569 bp) were analyzed by direct sequencing. Nucleotide variants were detected at 1488 sites in the 857 entire mtDNA sequences. A total of 311 variants were polymorphisms (minor allele frequency 1% in CON), and the frequencies of these polymorphisms were compared among the three groups. The EMA displayed excess of seven polymorphisms, including subhaplogroup D4e2- and D4g-specific polymorphisms, compared with CON (P<0.05), whereas SPA displayed excess of three polymorphisms and dearth of nine polymorphisms, including haplogroup G- and subhaplogroup G2a-specific polymorphisms, compared with CON (P<0.05). The frequencies of 10 polymorphisms, including haplogroup G- and subhaplogroup G2a-specific polymorphisms, were different between EMA and SPA (P<0.05): although none of these polymorphisms differed significantly between groups after correcting for multiple comparison (false discovery rate q-value 0.05). The number of rare variants in the 12S ribosomal RNA and NADH dehydrogenase subunit I genes were also higher in SPA than in CON (P<0.05). Analysis of the entire mtDNA of elite Japanese athletes revealed several haplogroup- and subhaplogroup-specific polymorphisms to be potentially associated with elite Japanese athletic status.

Analysis of functional variants in mitochondrial DNA of Finnish athletes

“…The ambient oxygen of 11% corresponding to 4000 m altitude resulted in amelioration of symptoms and longer survival compared to knock-out mice in atmospheric oxygen [41]. Our results, those showing that the frequency of rare variants in MT-ND1 is higher in Japanese sprinters than that in controls [14], and population genetic and experimental data on adaptation and survival in hypoxic environment suggest that haplogroup J mtDNA or m.4216 T > C may reduce the capacity of OXPHOS and induce glycolytic pathway that would be beneficial for sprint performance. Furthermore, it is worth mentioning that some of the variants defining haplogroup J are located in the mtDNA regulatory region and may have functional importance.…”

“…We propose that such mutations could be favorable to the function of OXPHOS. Indeed, previously Japanese endurance athletes have been found to harbor a subset of mitochondrial DNA rare variants, clustered in branches of haplogroup A3, possibly influencing elite athletic performance [14]. It should be also noted that rare mtDNA variants have been associated with physiological and clinical phenotypes related with endurance performance including regulation of blood pressure [15], vascular function [16], body mass index and waist-hip ratio [17].…”

Current Progress in Sports Genomics

“…7)) compared with controls. On the other hand, 85 sprint/power athletes showed greater frequency of the m.204C, m.151T, and m.15314A alleles and dearth of nine alleles (m.16278T, m.5601T, m.4833G, m.5108C, m.7600A, m.9377G, m.13563G, m.14200C, m.14569A) compared with controls[121,122].…”

Mitochondrial mutations alter endurance exercise response and determinants in mice

“…Most of the primary molecular mediators of an exercise stimulus are directly associated with the mitochondria. The relationship between exercise and mitochondria is demonstrated by the enrichment of African mtDNA lineage L0 in long-distance runners versus enrichment of Eurasian J, Uk, and F in sprinters ( 29 – 35 ). Consequently, mitochondrial mutations in PMDs might affect not only the exercise capacity but also the exercise response.…”