Association of mitochondrial DNA haplogroups J and K with low response in exercise training among Finnish military conscripts

Kiiskilä, Jukka; Jokelainen, Jari; Kytövuori, Laura; Mikkola, Ilona; Härkönen, Pirjo; Keinänen‐Kiukaanniemi, Sirkka; Majamaa, Kari

doi:10.1186/s12864-021-07383-x

Cited by 8 publications

(11 citation statements)

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“…Only one endurance athlete belonged to haplogroup J (1.9%), whereas the frequency of this haplogroup among sprinters was 6.7% and 4.8% for the controls. Similar findings were reported by Kiiskilä et al , 29 who genotyped a population-based cohort of Finnish military conscripts (1036). These participants had training activities such as combat skills, marching and sport-related physical training, and the endurance performance was assessed by the Cooper 12 min running test.…”

Section: Resultssupporting

confidence: 89%

Is there a mitochondrial DNA haplogroup connection between osteoarthritis and elite athletes? A narrative review

Pelletier

2022

RMD Open

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Elite athletes are at greater risk of joint injuries linked to the subsequent risk of developing osteoarthritis (OA). Genetic factors such as mitochondrial (mt) DNA haplogroups have been associated with the incidence/progression of OA and athletic performance. This review highlights an area not yet addressed: is there a common pattern in the mtDNA haplogroups for OA occurrence in individuals and elite athletes of populations of the same descent? Haplotypes J and T confer a decreased risk of OA in Caucasian/European descent, while H and U increase this risk. Both J and T haplogroups are under-represented in Caucasian/European individuals and endurance athletes with OA, but power athletes showed a greater percentage of the J haplogroup. Caucasian/European endurance athletes had a higher percentage of haplogroup H, which is associated with increased athletic performance. In a Chinese population, haplogroup G appears to increase OA susceptibility and is over-represented in Japanese endurance athletes. In contrast, in Koreans, haplogroup B had a higher frequency of individuals with OA but was under-represented in the endurance athlete population. For Caucasian endurance athletes, it would be interesting to evaluate if those carrying haplotype H would be at an increased risk of accelerated OA, as well as the haplogroup G in Chinese and Japanese endurance athletes. The reverse might be studied for the Korean descent for haplogroup B. Knowledge of such genetic data could be used as a preliminary diagnosis to identify individuals at high risk of OA, adding prognostic information and assisting in personalising the early management of both populations.

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Section: Resultssupporting

confidence: 89%

Is there a mitochondrial DNA haplogroup connection between osteoarthritis and elite athletes? A narrative review

Pelletier

2022

RMD Open

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“…When performing common and low-frequency MT-SNVs (MAF ≥ 0.01; n = 111) association analyses in these individuals, we observed that in HARD cases, no MT-SNVs survived multiple testing correction, the most significant (nominal p < 0.05) findings being for m.295C>T, m.12612A>G, m.12372G>A, m.11467A>G, m.15301G>A and m.7768A>G ( Table 2 and Figure 2 ). m.295C>T (rs41528348, p = 0.0118, MAF = 0.10) is a control region (CR) genetic variant tagging macro-haplogroup J, known to be associated with low maximal oxygen uptake (VO2max) in response to aerobic exercise [ 51 , 52 , 53 ] and thus cardiorespiratory fitness and CVD risk [ 54 , 55 , 56 , 57 ]. In line with this, a previous study in the UK Biobank [ 58 ] reported a significant association between m.295C>T and several blood cell traits ( Figure 5 ), known to increase with training [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

“…In SOFT cases, four MT-SNVs survived multiple testing correction (at FDR < 5%; Table 3 and Figure 3 ), all potentially conferring increased CAD risk: m.10400C>T, m.11251A>G, m.15452C>A and 15301G>A. m.11251A>G (rs869096886, p = 0.0011, MAF = 0.20) represents a synonymous sequence variant in the ND4 gene and m.15452C>A (rs193302994, p = 0.0017, MAF = 0.20) is a non-synonymous (Leu→Ile) sequence variant in the CYB gene; both were found more frequently in SOFT CAD cases vs. controls (OR = 1.03; 95% CI 1.01–1.05). m.11251A>G (rs869096886) and m.15452C>A (rs193302994) are tagging macro-haplogroup J and thus potentially related to a decreased cardiorespiratory fitness/exercise capacity [ 52 , 53 ] and increased CAD risk. Moreover, both MT-SNVs displayed significant associations with body height in the UK Biobank ( Figure 5 ) [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Examining the Association between Mitochondrial Genome Variation and Coronary Artery Disease

Vilne

Sawant

Rudaka

2022

Genes

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Large-scale genome-wide association studies have identified hundreds of single-nucleotide variants (SNVs) significantly associated with coronary artery disease (CAD). However, collectively, these explain <20% of the heritability. Hypothesis: Here, we hypothesize that mitochondrial (MT)-SNVs might present one potential source of this “missing heritability”. Methods: We analyzed 265 MT-SNVs in ~500,000 UK Biobank individuals, exploring two different CAD definitions: a more stringent (myocardial infarction and/or revascularization; HARD = 20,405), and a more inclusive (angina and chronic ischemic heart disease; SOFT = 34,782). Results: In HARD cases, the most significant (p < 0.05) associations were for m.295C>T (control region) and m.12612A>G (ND5), found more frequently in cases (OR = 1.05), potentially related to reduced cardiorespiratory fitness in response to exercise, as well as for m.12372G>A (ND5) and m.11467A>G (ND4), present more frequently in controls (OR = 0.97), previously associated with lower ROS production rate. In SOFT cases, four MT-SNVs survived multiple testing corrections (at FDR < 5%), all potentially conferring increased CAD risk. Of those, m.11251A>G (ND4) and m.15452C>A (CYB) have previously shown significant associations with body height. In line with this, we observed that CAD cases were slightly less physically active, and their average body height was ~2.00 cm lower compared to controls; both traits are known to be related to increased CAD risk. Gene-based tests identified CO2 associated with HARD/SOFT CAD, whereas ND3 and CYB associated with SOFT cases (p < 0.05), dysfunction of which has been related to MT oxidative stress, obesity/T2D (CO2), BMI (ND3), and angina/exercise intolerance (CYB). Finally, we observed that macro-haplogroup I was significantly (p < 0.05) more frequent in HARD cases vs. controls (3.35% vs. 3.08%), potentially associated with response to exercise. Conclusions: We found only spurious associations between MT genome variation and HARD/SOFT CAD and conclude that more MT-SNV data in even larger study cohorts may be needed to conclusively determine the role of MT DNA in CAD.

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“…In line with these earlier reports, our results show that m.295C>T was more frequent (OR=1.05; 95% CI 1.02-1.09, P=0.0118) in HARD cases, thus, potentially conferring a decreased cardiorespiratory fitness/exercise capacity and increased CAD risk. Of note, m.295C>T is also tagging macro-haplogroup J, and it has been previously shown that VO2max is lower in J than in non-J macro-haplogroup individuals [72] and excellence in endurance performance was less frequent among macro-haplogroup J individuals [52].…”

Section: Discussionmentioning

confidence: 99%

“…In SOFT cases, four MT-SNVs survived multiple testing correction (at FDR<5%; Table 3 and Fig.3), all potentially conferring increased CAD risk: m.10400C>T, m.11251A>G, m.15452C>A and 15301G>A. m.11251A>G (rs869096886, P=0.0011, MAF=0.20) represents a synonymous sequence variant in ND4 gene and m.15452C>A (rs193302994, P=0.0017, MAF=0.20) is a non-synonymous (Leu → Ile) sequence variant in CYB gene, both were found more frequently in SOFT CAD cases vs. controls (OR=1.03; 95% CI 1.01-1.05). m.11251A>G (rs869096886) and m.15452C>A (rs193302994) are tagging macro-haplogroups J and T, potentially related to a decreased cardiorespiratory fitness/exercise capacity [52, 72] and thus increased CAD risk, as discussed above. Moreover, both MT-SNVs displayed significant (P< 1e - 5) associations with body height in UK Biobank (Fig.5) [108].…”

Section: Discussionmentioning

confidence: 99%

Examining the Association between Mitochondrial Genome Variation and Coronary Artery Disease

Vilne

Sawant

Rudaka

2022

Preprint

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Background: Large-scale genome-wide association studies have identified hundreds of single-nucleotide variants (SNVs) significantly associated with coronary artery disease (CAD). However, collectively, these explain <20% of the heritability. Hypothesis: Here, we hypothesize that mitochondrial (MT) SNVs might present one potential source of this "missing heritability". Methods: We analyzed 265 MT-SNVs in ~500,000 UK Biobank individuals, exploring two different CAD definitions: a more stringent (myocardial infarction and/or revascularisation; HARD=20,405), and a more inclusive (also angina and chronic ischemic heart disease; SOFT=34,782). Results: In HARD cases, the most significant (P<0.05) associations were for m.295C>T (control region) and m.12612A>G (ND5), found more frequently in cases (OR=1.05), potentially related to reduced cardiorespiratory fitness in response to exercise, as well as for m.12372G>A (ND5) and m.11467A>G (ND4), present more frequently in controls (OR=0.97), previously associated with lower ROS production rate. In SOFT cases, four MT-SNVs survived multiple testing correction (at FDR<5%), all potentially conferring increased CAD risk. Of those, m.11251A>G (ND4) and m.15452C>A (CYB) have previously shown significant associations with body height. In line with this, we observed that CAD cases were slightly less physically active and their average body height was ~2.00 cm lower compared to controls, both traits known to be related to an increased CAD risk. Gene-based tests identified CO2 associated with HARD/SOFT CAD, whereas ND3 and CYB associated with SOFT cases (P<0.05), dysfunction of which has been related to MT oxidative stress, obesity/T2D (CO2), BMI (ND3) and angina/exercise intolerance (CYB). Finally, we observed that macro-haplogroup I was significantly (P<0.05) more frequent in HARD cases vs. controls (3.35% vs. 3.08%), potentially associated with response to exercise. Conclusions: We found only spurious associations between MT genome variation and HARD/SOFT CAD and conclude that more MT- SNV data in even larger study cohorts may be needed to conclusively determine the role of MT-DNA in CAD.

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Association of mitochondrial DNA haplogroups J and K with low response in exercise training among Finnish military conscripts

Cited by 8 publications

References 54 publications

Is there a mitochondrial DNA haplogroup connection between osteoarthritis and elite athletes? A narrative review

Is there a mitochondrial DNA haplogroup connection between osteoarthritis and elite athletes? A narrative review

Examining the Association between Mitochondrial Genome Variation and Coronary Artery Disease

Examining the Association between Mitochondrial Genome Variation and Coronary Artery Disease

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