Table 2.
Summary of findings from candidate gene studies
| Gene | Variant | Chromosome | Author & Date | Race | Age | Sex | Health concerns | (+/−/0)* Genotype & VO2max training response | P-value (x) | Highest training intensity | Sessions/week | Duration per session (min) | Training period | Training modality |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PPARGC1 | Intron 7G/C | 22 | Onkelinx, 2011 | 935 Caucasian | ~56 | M&F | Y (CAD) | GG, CG, CC (0) | 0.51 | 80% HRmax | 2–3 | 90 | 3 months | Ambulatory |
| He, 2008b | 102 Chinese | ~19 | M | N | All variants (0) | > 0.05 | 95–105% VT | 3 | Time to finish. | 18 weeks | 5000 m running | |||
| APOE | E2: rs7412 (c.526C > T; p.Arg176Cys) E3: WT E4: rs429358 (c.388 T > C; p.Cys130Arg) E3/E3: WT/WT E2/E3: p.Arg176Cys/WT E4/E3: p.Cys130Arg/WT E2/E2: p.Arg176Cys/p.Arg176Cys E2/E4: p.Arg176Cys/p.Cys130Arg E4/E4: p.Cys130Arg/p.Cys130Arg |
19 | Yu, 2014 | 360 Chinese | 18–40 | M F M F M&F |
N | E2/E3 in M (+) n = 20 E2/E3 F (+) n = 25 E3/E4 M (+) n = 31 E3/E4 F (+) n = 29 E2/E2; E2/E4; E3/E3; E4/E4 in M&F (0) |
0.04 0.03 0.02 0.02 > 0.05 |
60–85% VO2max | ‘Progressive’ but details NA | ‘Progressive’ but details NA | 6 months | Treadmill |
| Leon, 2004 | 265 Caucasian | 17–65 | M&F | N | All variants (0) | > 0.05 | 75% VO2max | 3 | 30–50 | 20 weeks | Cycle ergo | |||
| Thompson, 2004 | 170 Unknown | ~39 | M&F | N | E3/E3 (−) n = 43 E2/E3 (0) n = 40 E3/E4 (0) n = 41 |
< 0.01 | 60–85% VO2max | 4 | Up to 50 min | 6 months | Treadmill | |||
| CKM | 1170 & 985 + 185 | 19 | Defoor, 2005 | 935 Caucasian | ~56 | M&F | Y (CAD) | AA; GG; A/G (0) | > 0.05 | 80% HRmax | 2–3 | 90 | 3 months | Ambulatory |
| Rivera, 1999 | 240 Caucasian | 17–65 | M&F | N | CKM locus (n = 227) | < 0.01 | 75% VO2max | 3 | 30–50 | 20 weeks | Cycle ergo | |||
| Rivera, 1997 | 495 Caucasian | 17–65 | M&F | N | Homozygotes 1170bpa allele (−) n = 12 | < 0.05 | 75% VO2max | 3 | 30–50 | 20 weeks | Cycle ergo | |||
| Bouchard, 1989 | 295 Caucasian | 18–30 | M&F | N | All variants (0) | > 0.05 | 1. 60–85% HRR 2: 80–85% HRR |
1: 1–2 2: 3–5 |
1: Intervals 2: 30–45 |
1: 15 2: 15 |
1: Cycling 2: Cycling |
|||
| ACE | Insertion (I) or Deletion (D) | 17 | Alves, 2009 | 83 Brazilian | ~26 | M | N | All variants (0) | > 0.05 | 50–80% VO2peak | 2–3 | 60 min | 17 weeks | Running |
| Rankinen, 2000b | 476 Caucasian 248 AA |
17–65 | M&F | N | DD Caucasian offspring (+) n = 81 |
0.042 | 75% VO2max | 3 | 30–50 | 20 weeks | Ergo cycle | |||
| Defoor, 2006 | 935 Caucasian | ~56 | M&F | Y (CAD) | II (+) (frequency of 0.3 M and 0.36 F) | Entire group: 0.047 No Ace inhibitors: 0.013 |
80% HRmax | 2–3 | 90 | 3 months | Ambulatory | |||
| Woods, 2002 | 59 Caucasian | ~19 | M | N | II; I/D; DD (0) | >0.22 | NA | NA | NA | 11 weeks | Squads, adventure training, running, circuits | |||
| Sonna, 2001 | 147 Caucasian, 37 AA, 26 other | 19–24 | M&F | N | II, DD (0) | >0.05 | NA | 4–6 | 90 min | 8 weeks | Military training | |||
| CYBA; P22Phox | A24G – 640A > G | 16 | Onkelinx, 2011 | 935 Caucasian | ~56 | M&F | Y (CAD) | AA, AG, GG (0) CC, CT, TT (0) |
0.78 0.94 |
80% HRmax | 2–3 | 90 | 3 months | Ambulatory |
| PLIN | PLIN1 (6209 T > C) – rs2289487 15:g.90217096C > T PLIN4 (11482G > A) – rs894160 15:g.90211823C > T PLIN5 (13041A > G – rs2304795 15:g.90210263A > G PLIN6 (149954A > T – rs1052700 15:g.90208310A > T |
15 | Jenkins, 2010 | 101 Caucasian | NA | M&F | N | Genotypes and haplotypes (0) | p > 0.05 | Up to 70% VO2max | 3 | 20–40 min | 24 weeks | Multi-modal |
| AKT | rs1130214 (4:g.105259734C > A) | 14 | McKenzie, 2011 | 109 Caucasian | 50–75 | M F |
Elevated BP, cholesterol, menopause | All genotypes sig. Increased, but GT/TT men (+) n = 22 | 0.037 | 50–70%HRR | 3 | 20–40 min | 24 weeks | Multi-modal |
| HIF1A | T + 140C (rs11549465) A-2500 T |
Ch 14 | Prior, 2003 | 101 Caucasian 22 AA |
>60 <60 |
M&F | N | CT & TT in Caucasian over 60 (−) n = 37 All other ages, race and genotypes (0) |
0.03 >0.05 >0.05 |
50–70% VO2max | 3 | 20–40 min | 24 weeks | ‘Aerobic training’ |
| Na + −K + −ATPase α2 | Alpha2 exon 1 Alpha2 exon 21–22 |
13 | Rankinen, 2000a | 472 Caucasian | 17–65 | M&F | N | 3.3/3.3 (−) n = 5 10.5/10.5 offspring (+) n = 14 |
0.018 0.017 |
55–75% VO2max | 3 | 30–50 | 20 weeks | Cycle ergo |
| HBB | -551C/T – no rs ID 11:g.5248801 T > C +16, intron 2 - rs10768683 11:g.5247791C > G +340 – no rs ID 11:g.5246488 T > A |
11 | He, 2006 | 102 Chinese | ~19 | M | N | CC, CT, TT (0) CC, CG, GG (0) AA, AT, TT (0) |
>0.05 | 95–105% VT | 3 | Time to finish. | 18 weeks | 5000 m running |
| CNTF | rs1800169 (11:g.58391501G > A) | 11 | Thomaes, 2011 | 935 Caucasian | ~56 | M&F | N | AA (+) n = 21 | 0.002 | 80% HR max | 2–3 | 90 | 3 months | Ambulatory |
| CAT | -262C > T | 11 | Onkelinx, 2011 | 935 Caucasian | ~56 | M&F | Y (CAD) | TT (−) n = 342 | 0.02 | 80% HR max | 2–3 | 90 | 3 months | Ambulatory |
| GSTP1 | rs1695 (11:g67352689A > G c.313A > G p.Ile105Val) |
11 | Zabreska, 2014 | 66 Polish | 19–24 | F | N | GG & AG (+) n = 30 | Absolute: 0.029 Relative: 0.025 |
50–75% HR max | 3 | 60 | 3 months | ‘Aerobic routine’ |
| ADRB1 | Pos. 145 Pos. 1165 |
10 | Defoor, 2006 | 935 Caucasian | ~56 | M&F | Y(CAD) | Ser49Gly49, Ser49Ser49, | 80% HR max | 2–3 | 90 | 3 months | Ambulatory | |
| Gly49Gly49 (0) GLy389Gly389, |
0.18 | |||||||||||||
| Gly389Arg389, Arg389Arg389 (0) | 0.75 | |||||||||||||
| TFAM | rs1937 (10:g.60145342G > C c.35G > C p.Ser12Thr) rs2306604 (10:g.60148692A > G) rs1049432 (10:g.60155120G > T) |
10 | He, 2007b | 102 Chinese | ~19 | M | N | GG, CG, CC (0) AA, AG, GG (0) GG, GT, TT (0) |
>0.05 | 95–105% VT | 3 | Time to finish. | 18 weeks | 5000 m running |
| NOS3 | T-1495A – No rs ID 7:g.150689397A > T A-949G – rs1800779 7:g.150689943G > A -786 T > C– rs41322052 7:g150690106C > T G298A – rs1799983 7:g.150696111 T > G c.894 T > G (p.Asp298Glu)) |
7 | Onkelinx, 2011 | 935 Caucasian | ~56 | M&F | Y (CAD) | TT, TA, AA (0) AA, AG, GG (0) TT, TC, CC (0) TT, CT, C (0) CC, CT, TT (0) GG, GA, AA (0) |
0.54 0.76 0.69 0.69 1.88 1.04 |
80% HRmax | 2–3 | 90 | 3 months | Ambulatory |
| -786 T > C– rs41322052 7:g150690106C > T Intron 4 – rs61722009 VNTR (repeat) 7:g.150694276_150694302AGGGGTG 894G > T – rs1799983 7:g.150696111 T > G c.894 T > G (p.Asp298Glu)) |
7 | Silva, 2011 | 80 Portuguese | 20–35 | M | N | TT, CC, TC (0) 4b4b, 4ba4c, 4a4a (0) GG, GT, TT (0) *All genotypes sig. Increased. fitness, thus no difference between groups |
0.001 | Graded to VT HR | 3 | 80 min | 18 weeks | Running | |
| NRF-1 | C&T - rs2402970 7:g.80647382G > T A & G - rs10500120 7:g.129393341A > G rs6949152 7:g129286436A > G |
7 | He, 2008a | 102 Chinese | ~19 | M | N | CC, CT, TT (0) AA, AG, GG (0) AA, AG, GG (0) |
0.38 0.110 0.094 |
95–105% VT | 3 | Time to finish. | 18 weeks | 5000 m running |
| AK1M | common and rare variants | 7 | Bouchard, 1989 | 295 Caucasian | 18–30 | M&F | N | (0) | > 0.05 | 1. 85% HRR 2: 85% HRR |
1: 1–2 2: 3–5 |
1: Intervals 2: 30–45 |
1: 15 2: 15 |
1: Cycling 2: Cycling |
| PPARD | Exon 4 + 15 Exon 7 + 65 |
Ch 6 | Hautala, 2007 | Caucasian AA | 17–65 | M&F | N | CC genotype in AA of Exon 4 + 15 (−) n = 19 | 0.005 | 75% VO2max | 3 | 30–50 | 20 weeks | Cycle ergo |
| VEGF | 405 460 |
6 | Onkelinx, 2011 | 935 Caucasian | ~56 | M&F | Y (CAD) | GG, GC, CC (0) CC, CT, TT (0) |
0.52 0.52 |
80% HR max | 2–3 | 90 | 3 months | Ambulatory |
| GR/NR3C1 | rs6190 (5:g.142780337C > T c.68G > A p.Arg23Lys) |
5 | Thomaes, 2011 | 935 Caucasian | ~56 | M&F | Y (CAD) | G/A (+) n = 55 | <0.01 | 80% HR max | 2–3 | 90 | 3 months | Ambulatory |
| PPARα | Gly482Ser | 4 | Onkelinx, 2011 | 935 Caucasian | ~56 | M&F | Y (CAD) | GG, G, SS (0) | 0.59 0.8 |
80% HR max | 2–3 | 90 | 3 months | Ambulatory |
| SOD3 | C760G | 4 | Onkelinx, 2011 | 935 Caucasian | ~56 | M&F | Y (CAD) | CC (0) G carrier (0) |
0.12 0.18 |
80% HR max | 2–3 | 90 | 3 months | Ambulatory |
| GPX | 197P > L | 3 | Onkelinx, 2011 | 935 Caucasian | ~56 | M&F | Y(CAD) | Pro197Pro (0) Leu-carrier (0) |
0.18 0.78 |
80% HR max | 2–3 | 90 | 3 months | Ambulatory |
| NFE2L2 | Rs125949 Rs8031031 Rs718186 |
2 | He, 2007b | 102 Chinese | ~19 | M | N | CC, CA, AA (0) CT, TT, AA (0) AG, GG (0) |
> 0.05 | 95–105% VT | 3 | Time to finish. | 18 weeks | 5000 m running |
| AMPD1 | AMPD1:c.133C (rs17602729) | 1 | Thomaes, 2011 | 935 Caucasian | ~56 | M&F | N | CC (+) n = 652 | < 0.05 | 80% HR max | 2–3 | 90 | 3 months | Ambulatory |
| Rico-Sanz, 2003 | 329 Caucasian 90 AA |
17–65 | M&F | N | TT (−) in Caucasians (n = 6) | < 0.006 | 75% VO2max | 3 | 30–50 | 20 weeks | Cycling | |||
| mtDNA | MTND5 m.13470A > C or A > G m.12406G > A m.13365C > T |
mtDNA SNP via restriction enzyme | Murakami, 2001 | 21 Japanese | 20.6 | M | N | All variants (0) | > 0.05 | 70% VO2max | 3–4 | 60 min | 8 weeks | Ergo Cycle |
| mtDNA | Within mitochondria | Dionne, 1991 | 53 Quebec, Tempe | 17–27 | M | N | mtDNA subunit 5 N5 (−) n = 3 | 0.05 | Quebec: 85% HRR Tempe:77% VO2max |
Quebec: 3 Tempe: 3–5 |
Quebec:45 min Tempe:40 min |
Quebec: 20 wks Tempe: 12 wks |
Ergo Cycle | |
| ALAS2 | ≤166 bp | Mitochondria | Xu, 2015 | 72 Chinese | 18–22 | M | N | ≤166 bp (+) n = 25 | < 0.05 | ‘High/Low training’ | 3 | 30 min | 4 weeks | Ergo Cycle |
where possible, gene variants were annotated using the references sequence (GRCh37/hg19)
CAD coronary artery disease, wks weeks, mths months, VO 2max maximal oxygen uptake/cardiorespiratory fitness, AT anaerobic threshold, HRR heart rate reserve, HRmax heart rate maximum, Pmax maximal aerobic power, Cauc Caucasian, AA African-American, M male, F female
**(+) = high training response, (−) = low training response, (0) = neutral training response
(x) = p-value has been adjusted for covariates except for article by Xu et al. (2015) where it wasn’t clear if p-value had been adjusted (ALAS2)