Table 1 Summary of included articles

Xu, 2015, China

ALAS2

Single group, longitudinal. VO_2max and venous blood samples taken pre & post intervention.

N = 244 healthy Chinese males; 18-22 years (20 ± 1.76); wt 65.06 ± 9.59 kg; ht. 174.37 ± 6.16 cm. N = 72 randomly selected for HiHiLo training (69.8 ± 7.8 kg and 177.93 ± 5.26 cm).

Peripheral blood leucocytes

PCR protocol + separation on polyacrylamide gel

4 weeks; supervised HiLo training in hypoxia-training centre. Hi = bicycle ergometer for 30 mins at 75% VO_2max, in 15.4% O₂ concentrated environment, 3×/week for 4 weeks. Lo = same training but at lower elevation.

Yu, 2014, China

APOE

Single group, longitudinal. VO_2max, anthropometric and serum levels tested pre & post intervention.

N = 360; 180 Chinese males and females; age 32.8 ± 11.9 yrs.; BMI 25.4 ± 5.6 kg/m² M; BMI 26 ± 6.2 kg/m² F; no health concerns; inactive.

Peripheral blood leucocytes

PCR-(polymerase chain reaction)-RFLP (restriction fragment length polymorphism) assay

6 mths; progressive; supervised aerobic training; 60–85% VO_2max.

Zarebska, 2014, Poland

GSTP1

Single group, longitudinal. VO_2max, HR_max, VE_max, AT and body composition tested pre & post intervention; balanced diet prior to intervention (2000 kcal)

N = 66 Polish females; 19–24 yrs.; BMI 21.8 ± 2.1 kg/m²; no health concerns; inactive; no supplements or medications; non-smokers.

Buccal cells

TaqMan allelic discrimination assay using qPCR

3 mths; supervised; progressive MICT; 3×/wk.; 50–75% HR_max; 30–60 min.

Ghosh, 2013, Singapore

GWAS

Retrospective, single-group longitudinal. V0_2max tested pre & post intervention.

HERITAGE WHITES: n = 473 Caucasians; 230 male & 243 females; no major health concerns; inactive.

Lymphoblastoid cell lines

Illumina Human CNV370-Quad Bead Chips

HERITAGE: 20 wks; supervised; progressive MICT; 3×/wk.; 55–75% VO_2max; 30–50 min.

Bouchard, 2011, USA

GWAS

Retrospective HERITAGE: Single group, longitudinal; VO_2max tested pre & post intervention. DREW: RCT; VO_2max tested pre & post intervention. STRRIDE 1 & 2: RCT; VO_2max tested pre & post intervention.

HERITAGE WHITES: n = 473 Caucasians (252 women); 17–65 yrs.; inactive; no major health concerns

HERITAGE BLACKS: n = 259 (177 women); 17–65 years; inactive; no major health concerns

HERITAGE average age = 35.7 ± 14.5 yrs., BMI 25.8 ± 4.9 kg/m².

DREW study: n = 464 overweight or obese postmenopausal women; inactive; no major health concerns.

STRRIDE 1 study: M&F; 40–65 yrs.; inactive; overweight, dyslipidemic and postmenopausal (F).

STRRIDE 2 study: 18–70 yrs.; inactive; overweight, dyslipidemic. N = 183 for STRRIDE 1&2 studies.

Lymphoblastoid cell lines

Illumina Human CNV370-Quad Bead Chips

HERITAGE

20 wks; supervised; progressive, MICT; 3×/wk.; 55–75% VO_2max; 30–50 min.

DREW: 6 mths; supervised; exercise groups: 4, 8 or 12 kcal/kg/week (MICT); 3-4×/week; progressive training intensity started at 50% VO_2max. Each group expended 4 kcal/kg/week for first week.

Group 1: maintained 4 kcal/kg/week for 6 months. Group 2: increased by 1 kcal/kg/week until 8ckal/week reached – maintain for remaining time. Group 3: increased by 1 kcal/kg/week until 8ckal/week reached – maintain for remaining time.

STRRIDE 1: 8–9 mths; supervised exercise sessions. Three groups: 1. High-amount/vigorous intensity exercise (170 min/week/2000 kcal/week) or the calorie equivalent of jogging for ~20 miles per week at 55–85% VO_2max.

2. Low amount/vigorous-intensity exercise/1200 kcal/week (~120 min/week) or the equivalent of 12 miles/week for jogging at 65–80%.

3. Low amount, moderate intensity exercise (1200 kcal/week (170 min/week) or the equivalent of 12 miles/week at 40–55% VO_2max.

STRRIDE 2: 8–9 mths; supervised; four groups:

1: Aerobic training – 1300 cal – 65-80%; 2: Resistance training only with 3 sets of 12–15 reps 3 x /week. 3: Combination of the first 2 protocols; 4: High anaerobic training – 2200 cal – 3 x week – 65-80%. First 2–3 months ‘ramp up period’. Following 6 mths using appropriate protocol.

McKenzie, 2011, USA

AKT

Single group, longitudinal. VO_2max tested pre & post intervention; dietary stabilisation.

N = 51 M and 58 F Caucasians; 50–75 yrs.; no major health concerns; non-smoking; BMI <37; haematocrit >35; BP between 120/80 but less than 160/100 mmHg; at least one lipid abnormality; not any medication for blood pressure, cholesterol or glucose; F post-menopausal for at least 2 years (stable HRT or non HRT); inactive.

Peripheral blood leucocytes

TaqMan allelic discrimination assay using qPCR

24 wks; supervised; progressive MICT; 3×/wk.; 50–70% HRR; 20–40 min.

Thomaes, 2011, Belgium

AMPD1; GR; CNTF

Retrospective, single group, longitudinal. VO_2peak tested pre & post intervention.

N = 935 coronary artery disease patients (CAD); 76 females; Caucasian; age 56 ± 0.3 yrs.; BMI 25.8 ± 0.1 kg/m²; 5% smokers; 85% cardiac medications; 5% diabetes; 27% hypertension.

Peripheral blood leucocytes

Invader TM assay (third wave technologies)

3 mths; supervised; 2-3×/wk.; 80% HR_max; 90 mins/session.

Onkelinx, 2011, Belgium

NOS3; Catalase; VEGF; Eco-SOD; GPX; P22Phox; PPARGC1; PPARα

Retrospective, single group, longitudinal. VO_2peak tested pre & post intervention.

N = 935 coronary artery disease patients (CAD); 76 females; Caucasian; age 56 ± 0.3 yrs.; BMI 25.8 ± 0.1 kg/m²; 5% smokers; 85% cardiac medications; 5% diabetes; 27% hypertension.

Peripheral blood leucocytes

Invader TM Assay (third wave technologies)

CARAGENE: 3 mths; supervised; 3×/week; 90 mins; ~ intensity = 80% (HR/peakHRx100)

Silva, 2011, Brazil

NOS3

Single group, longitudinal. VO_2peak tested pre & post intervention.

N = 80 Portuguese police recruits; 20–35 years; BMI 23.3 ± 3.6 kg/m²; no health concerns; inactive.

Peripheral blood leucocytes

PCR-RFLP

18 weeks; supervised; 3×/week/ 80 mins; intensity graded to VT HR.

Timmons, 2010, UK

GWAS

1: Single group, longitudinal. VO_2max & muscle biopsies tested pre & post intervention; 2: Blind test. VO_2max & muscle biopsies tested pre & post intervention; 3: Retrospective: HERITAGE WHITES data

1: N = 24 sedentary healthy Caucasian men (23 ± 1 yrs., 1.82 ± 0.02 m, 78.6 ± 2.7 kg); 2: 17 active & healthy Caucasian men (29 ± 6 yrs., 81.8 ± 9 kg, 1.8 ± 0.5 m); 3: HERITAGE Caucasians (as described in Bouchard 2011).

Lymphoblastoid cell lines from venous blood

Illumina Human CNV370-Quad Bead Chips

1: 6 weeks; supervised MICT; 4 × 45 min cycling sessions/week @ 70% VO_2max.

2:12 weeks; cycle ergometer 5×/week. Peak power test performed every Mon to determine intensity for week: Tues: 3 min intervals at 85%. P_max separated by 3 min intervals at 40% P_max; Thurs: 8 min intervals at 85% P_max separated by 3 min intervals at 40% P_max; Fri: 120 min at 55% P_max continuously; duration increased by 5%/wk.; last 6 wks duration maintained but intensity increased by 1%/week; 3: HERITAGE WHITES Study (as described in Bouchard 2011).

Jenkins, 2010, USA

PLIN haplotypes

Retrospective, single group, longitudinal. VO_2max tested; body composition; pre & post intervention; dietary stabilisation (American Heart Association).

N = 46 M & 55 F Caucasians (50–75 years); inactive; no major health concerns; BP < 160/99; non-smokers; BMI < 37 kg/m²; no meds for BP, cholesterol or glucose control; at least one lipid abnormality.

Unknown

TaqMan allelic discrimination assay using qPCR

24 weeks; supervised; multi-modal MICT; progressive; 3×/wk.; 20–40 min; up to 70% VO_2max reached; 60 min walk home included post 12 wks.

Alves, 2009, Brazil

ACE & Angiotensin

Single group, longitudinal. VO_2max and echocardiography of left ventricle pre and post intervention.

N = 83 Brazilian policemen; age 26 years ±4.5; BMI 24 kg/m² ± 1; healthy; normotensive.

Unknown

Polymerase chain reaction protocol.

17 weeks; supervised MICT; 50–80%VO_2peak; 60 min × 3/week.

He, 2008a, China

NRF-1

Single group, longitudinal; VO_2max, VT and RE tested pre & post intervention.

N = 102 Chinese male soldiers; no health concerns; age 18.8 ± 0.9 yrs.; wt 60.3 ± 6.5 kg; ht. 1.71 ± 5.8 m; no medications; non-smokers.

Peripheral blood leucocytes

PCR-RFLP assay

18 wks; supervised; 3×5000m running sessions/wk.; 95%–105% VT.

He, 2008b, China

PPARGC1

Single group, longitudinal; VO_2max, VT and RE tested pre & post intervention.

N = 102 Chinese male soldiers; no health concerns; age 18.8 ± 0.9 yrs.; wt 60.3 ± 6.5 kg; ht. 1.71 ± 5.8 m; no medications; non-smokers.

Peripheral blood leucocytes

PCR-RFLP assay

18 wks; supervised; 3×5000m running sessions/wk.; 95%–105% VT.

He, 2007a, China

TFAM

Single group, longitudinal. VO_2max, VT and RE tested pre & post intervention.

N = 102 Chinese male soldiers; no health concerns; age 18.8 ± 0.9 yrs.; wt 60.3 ± 6.5 kg; ht. 1.71 ± 5.8 m; no medications; non-smokers.

Peripheral blood leucocytes

PCR-RFLP assay

18 wks; supervised; 3×5000m running sessions/wk.; 95%–105% VT.

He, 2007b, China

NRF-2/NFE2L2

Single group, longitudinal. VO_2max, VT and RE tested pre & post intervention.

N = 102 Chinese male soldiers; no health concerns; age 18.8 ± 0.9 yrs.; wt 60.3 ± 6.5 kg; ht. 1.71 ± 5.8 m; no medications; non-smokers.

Peripheral blood leucocytes

PCR-RFLP assay

18 wks; supervised; 3×5000m running sessions/wk.; 95%–105% VT.

Hautala, 2007, USA

PPARD

Retrospective, single group, longitudinal. VO_2max, body composition and lipids tested pre & post intervention.

N = 477 from HERITAGE Caucasian study (183 female)

N = 264 from HERITAGE African-American study (247 female)

Unknown

SNP scorer genotyping software

20 wks; supervised; progressive, MICT; 3×/wk.; 55–75% VO_2max; 30–50 min.

Defoor, 2006a, Belgium

ADRB1

Retrospective, single group, longitudinal. VO_2peak tested pre & post intervention.

N = 935 coronary artery disease patients (CAD); 76 females; Caucasian; age 56 ± 0.3 yrs.; BMI 25.8 ± 0.1 kg/m²; 5% smokers; 85% cardiac medications; 5% diabetes; 27% hypertension.

Peripheral blood leucocytes

Invader assay

CARAGENE: 3 mths; supervised; 2-3×/wk.; 80% HR_max; 90 mins/session.

Defoor, 2006b, Belgium

ACE

Retrospective, single group, longitudinal. VO_2peak tested pre & post intervention.

N = 935 coronary artery disease patients (CAD); 76 females; Caucasian; age 56 ± 0.3 yrs.; BMI 25.8 ± 0.1 kg/m²; 5% smokers; 85% cardiac medications; 5% diabetes; 27% hypertension.

Peripheral blood leucocytes

Invader assay

CARAGENE: 3 mths; supervised; 2-3×/wk.; 80% HR_max; 90 mins/session.

He, 2006, China

HBB

Retrospective, single group, longitudinal. VO_2max, VT and RE tested pre & post intervention.

N = 102 Chinese male soldiers; no health concerns; age 18.8 ± 0.9 yrs.; wt 60.3 ± 6.5 kg; ht. 1.71 ± 5.8 m; no medications; non-smokers

Peripheral blood leucocytes

PCR-RFLP assay

18 wks; supervised; 3x5000m running sessions/wk.; 95%–105% VT

Defoor, 2005

CKMM

Retrospective, single group, longitudinal. VO_2peak tested pre & post intervention.

N = 935 coronary artery disease patients (CAD); 76 females; Caucasian; age 56 yrs. ± 0.3; BMI 25.8 kg/m² ± 0.1; 5% smokers; 85% cardiac medications; 5% diabetes; 27% hypertension.

Peripheral blood leucocytes

Invader assay

CARAGENE: 3 mths; supervised; 2-3×/wk.; 80% HR_max; 90 mins/session.

Leon, 2004, USA

APOE

Retrospective, single group, longitudinal. VO_2max, blood lipids tested pre & post intervention; counselled not to alter health habits.

N = 241 male and 89 female HERTIAGE Caucasians; 17–65 years; inactive; no major health concerns

Lymphoblastoid cell lines from venous blood

PCR-RFLP assay

HERTIAGE: 20 wks; supervised; progressive MICT; 3×/wk.; 55–75% VO_2max; 30–50 min.

Thompson, 2004, USA

APOE

Single group, longitudinal. VO_2max, anthropometric data and lipid levels collected pre & post intervention; dietary control.

N = 170 Caucasians (120 completed program – 60 M and F); 18–70 years (39 ± 11 years); consumed less than 2 drinks/day; physically inactive; BMI <31; no major health concerns.

Peripheral blood leucocytes

PCR-RFLP assay

6 months supervised progressive training; 60–80% of VO_2max; increasing from 15 to 40 mins during first 4 wks. Once at 40 mins, maintained this for 4 sessions each week for 5–6 months. Multimodal but treadmill primary aerobic activity.

Rico-Sanz, 2003, Canada

AMPD1

Retrospective, single group, longitudinal. VO_2max, submax and submax to maximal tested pre & post intervention.

N = 329 HERTAGE Caucasians and 90 HERITGAE African-Americans measured for training response; 17–65 years; inactive; no major health concerns.

Unknown

PCR protocol + separation on agarose gels

HERITAGE: 20 wks; supervised; progressive MICT; 3×/wk.; 55–75% VO_2max; 30–50 min

Prior, 2003, USA

HIF1A

Single group, longitudinal. VO_2max tested pre & post intervention.

N = 101 Caucasian and 22 African-Americans in good health; age 57.7 ± 0.91 yrs.; BMI 29.2 ± 0.64 kg/m²

Peripheral blood lymphocytes

PCR-RFLP assay

24 weeks; supervised; progressive MICT; 3×/wk.; 20–40 min; 50–70% VO_2max

Woods, 2002, UK

ACE

Single group, longitudinal. VO_2max, and HR/VO₂ relationship tested pre & post intervention.

N = 59 Caucasians with ACE II allele and 29 without ACE DD allele; ~age 18.9 yrs.; ~ht. 1.78 m; ~ wt 73.4 kg; military camp.

Peripheral blood leucocytes

PCR protocol + polyacrylamide gel separation

11 weeks; supervised aerobic training; 75% squads; 35% adventurous training; 25% running and circuit training.

Murakami, 2001, Japan

MtDNA

Single group, longitudinal. VO_2max tested pre & post intervention

N = 41 Japanese M (age 20.6 ± 2.2 yrs), inactive; no major health concerns; wt 62.8 ± 7.5 kg; ht. 171.8 ± 6.7 cm.

Peripheral blood leucocytes

PCR-RFLP assay

8 weeks; supervised 1×/week out of 3.5; 60 min/session; 70% VO_2max

Sonna, 2001, USA

ACE

Double-blind study. VO_2peak, anthropometrics physical fitness assessment for active duty personnel tested pre and post intervention.

N = 85 F and 62 M; age 21.7 ± 3.6 yrs.; 84 Caucasian, 20 Hispanic, 1 Native Americans, 5 Asian and 37 African-American; no major health concerns; BMI 23.1 ± 3.1 kg/m²; BF% 27.9 ± 6.1 F and 16.4 ± 5.7 M.

Peripheral blood leucocytes

PCR-RFLP assay

8 weeks supervised; 6 days/week; 2 x aerobic (sprints & 3–5 miles) & 2 x strength. Participants place in 1 of 4 ability groups so all running for same duration. Participants also completed road marches and other drills.

Rankinen, 2000a, USA

Na + −K + ATPaseα

Retrospective, single group, longitudinal. VO_2max and max power output tested pre & post intervention.

HERITAGE WHITES: 472 Caucasians; 17–65 years; inactive; no major health concerns.

Lympohblastoid cell lines

PCR protocol + agarose gel separation

HERTIAGE: 20 wks; supervised; progressive MICT; 3×/wk.; 55–75% VO_2max; 30–50 min

Rankinen,2000b, USA

ACE

Retrospective, single group, longitudinal. V0_2max, VE, VT, blood lactate, oxygen, stroke volume, carbon dioxide, HR, tested pre & post intervention (submax VO₂ test for older patients).

HERITAGE WHITES AND BLACKS: 476 Caucasian & 248 Blacks; 17–65 years; inactive; no major health concerns.

Lympohblastoid cell lines

PCR protocol + agarose gel separation

HERTIAGE: 20 wks; supervised; progressive MICT; 3×/wk.; 55–75% VO_2max; 30–50 min

Hagberg, USA, 1999

APOE

Retrospective, single group, longitudinal. VO_2max and lipid levels tested pre and post; stabilised on American Heart Association diet 8 weeks prior to intervention.

N = 51; 40–80-year-old sedentary men (61 ± 3 yrs); overweight with ~BF% 30 ± 3; BP < 160/95 mmHg; no major health concerns or medications for blood lipids or glucose.

Peripheral blood leucocytes

PCR-RFLP assay

9 months’ endurance training; multimodal; 5–7 months supervised and last 2–4 months used heart rate monitor to ensure 70–80% VO_2max intensity and 3 days/week for 45 min was complied with.

Rivera, 1999, Canada

CKMM

Retrospective, single group, longitudinal. VO_2max tested pre & post intervention.

HERITAGE WHITES: 495 Caucasians from 98 families; 17–65 years; inactive; no major health concerns.

Lympohblastoid cell lines

PCR-RFLP assay

HERTIAGE: 20 wks; supervised; progressive MICT; 3×/wk.; 55–75% VO_2max; 30–50 min

Rivera, 1997, Canada

CKMM

Retrospective, single group, longitudinal. VO_2max tested pre & post intervention.

HERITAGE WHITES: 160 Caucasian parents and 80 offspring; 17–65 years; inactive; no major health concerns.

Lympohblastoid cell lines

PCR-RFLP assay

HERTIAGE: 20 wks; supervised; progressive MICT; 3×/wk.; 55–75% VO_2max; 30–50 min

Dionne, 1991, Canada

mtDNA

Single group, longitudinal. VO_2max tested pre & post intervention.

N = 46 M from Quebec (17–27 yrs) & 27 M from Tempe (24–29 yrs); inactive

Peripheral blood leucocytes

PCR-RFLP assay

Quebec: 20 weeks; supervised; progressive training; Max 85% HRR; max 45 min/session; 3×/wk.

Tempe: 12 weeks; supervised; progressive training; max 70–77% VO_2max; max 40 min/session; 3×/wk

Bouchard, 1989, Canada

AK1M

CKM

RCT. VO2max, total power output tested pre & post intervention.

N = 295 M 7 F (18–30 years); healthy Caucasians

Muscle biopsy and peripheral blood leucocytes

Formazan technique?

Group 1: 15 weeks; supervised; progressive MICT; 30–45 min/session; 3-5×/wk.; 60–85% HRR

Group 2: 15 weeks; supervised; progressive interval training; 1-2×/week; 80–85% HRR separated by 5 min recovery.