Table 2.
Summary of genes involved in acute heart rate increase
| Gene | Variant | Chromosome/position | Minor/major allele/MAF | Type of study | Increase/decrease | P value | Type of exercise test | Population | Author; year |
|---|---|---|---|---|---|---|---|---|---|
| ACE a | Del intron 16 | 17:63488529 | Deletion/insertion | Candidate | – | > 5.00 × 10−2 | Maximal and submaximal bicycle | General | Rankinen et al. (2000) [25] |
| ADRA1A | rs544215 | 8:26712028 | C/T/0.46 | Candidate | ↓ | 5.00 × 10−3 | Standard Bruce | General | Ingelsson et al. (2007) [12] |
| ADRA1D | rs3787441 | 20:4205059 | G/A/0.27 | Candidate | ↓ | 7.00 × 10−3 | Standard Bruce | General | Ingelsson et al. (2007) [12] |
| ADRB1 | rs1801253 | 10:114045297 | C/G/0.28 | Candidate | ↓ | < 5.00 × 10−2 | Maximal | Patients in cardiac rehab | Defoor et al. (2005) [29] |
| ADRB1 | rs1801252 | 10:114044277 | G/A/0.21 | Candidate | ↓ | < 5.00 × 10−2 | Maximal | Patients in cardiac rehab | Defoor et al. (2005) [29] |
| ADRB2 | rs1042713 | 5:148826877 | A/G/- | Candidate | ↓ | < 5.00 × 10−2 | Hand grip test | General | Eisenach et al.(2003)[30] |
| CAV2 | rs28495552 | 7:116113744 | C/G/0.50 | GWAS | ↓ | 2.80 × 10−11 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| CCDC141 | rs10497529 | 2:179839888 | A/G/0.04 | GWAS | ↑ | 2.50 × 10−9 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| GNAS1 b | rs7121 | 20:58903752 | C/T/0.37 | Candidate | ↑ | <5.00 × 10−2 | Ergometer | Referred for exercise test | Nieminen et al. (2006) [28] |
| HMGA2 | rs1480470 | 12:66412130 | A/G/0.37 | GWAS | ↑ | 3.40 × 10−08 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| MCTP2 | rs12906962 | 15:95312071 | C/T/0.32 | GWAS | ↓ | 3.50 × 10−13 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| MCTP2 | rs12906962 | 15:95312071 | C/T/0.33 | GWAS | ↓ | 2.70 × 10−14 | Submaximal bicycle | General | Verweij et al. (2018) [14] |
| NOLA c,d | rs6847149 | 4:111157701 | – | GWAS | – | 2.74 × 10−06 | Standard Bruce | General | Vasan et al. (2007) [34] |
| NOS3 e | rs1799983 | 7:150999023 | T/G/0.26 | Candidate | ↓ | 4.00 × 10−2 | Naughton protocol | Post-menopausal women | Hand et al. (2006) [26] |
| PAX2 | rs11190709 | 10:102552663 | G/A/0.12 | GWAS | ↑ | 1.30 × 10−11 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| POP4 | rs12986417 | 19:30109533 | A/G/0.35 | GWAS | ↓ | 1.00 × 10−9 | Submaximal bicycle | General | Verweij et al. (2018) [14] |
| POP4 | rs7255293 | 19:30104198 | G/A/0.42 | GWAS | ↓ | 3.20 × 10−9 | Submaximal bicycle | General | Ramirez et al.(2018)[15] |
| PPIL1 | rs236352 | 6:36817113 | A/G/0.34 | GWAS | ↑ | 6.40 × 10−10 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| RGS6 | rs17180489 | 14:72885471 | C/G/0.14 | GWAS | ↑ | 2.50 × 10−11 | Submaximal bicycle | General | Verweij et al. (2018) [14] |
| RNF220 | rs272564 | 1:45012273 | C/A/0.28 | GWAS | ↓ | 7.40 × 10−12 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| RP1L1 | rs58065122 | 8:10526186 | A/G/0.42 | GWAS | ↑ | 3.90 × 10−10 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| RYR2 c,d | rs2819770 | 1:234237045 | – | GWAS | – | 3.53 × 10−6 | Standard Bruce | General | Vasan et al. (2007) [34] |
| SCN10A | rs7433723 | 3:38784957 | G/A/0.42 | GWAS | ↓ | 4.50 × 10−8 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| SNCAIP | rs4836027 | 5:121866990 | C/T/0.32 | GWAS | ↓ | 1.70 × 10−15 | Submaximal bicycle | General | Verweij et al. (2018) [14] |
| SNCA1P | rs4836027 | 5:121866990 | C/T/0.31 | GWAS | ↓ | 9.90 × 10−21 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| SOX5 | rs4246224 | 12:24784139 | A/G/0.15 | GWAS | ↑ | 1.80 × 10−14 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| SYT10 | rs1343676 | 12:33537387 | T/C/0.51 | GWAS | ↓ | 1.50 × 10−11 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
| TCF4 | rs1125313 | 18:52859261 | C/A/0.50 | GWAS | ↑ | 3.90 × 10−9 | Submaximal bicycle | General | Ramirez et al. (2018) [15] |
Genes found to be associated with heart rate increase during exercise are shown in alphabetical order and are then ordered on the year published. Variation stands for either an SNP or deletion/insertion mutation. MAF stands for Minor Allele Frequency. Effects of a variant (in- or decrease) on heart rate increase during exercise are shown for the Minor Allele. Candidate stands for candidate gene study. GWAS stands for genome-wide association study. A hyphen is shown in case information which was not reported
aResults from only one candidate gene study on ACE are shown; largest study was chosen; G allele in case of deletion; in case of insertion ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC
bStatistics from gene time of exercise interaction are showed
cStandard Bruce protocol is a maximal exercise treadmill test
dStatistics from the generalized estimating equations (GEE) tests are shown; Alleles were not mentioned in this article. None reached genome-wide significance; however, these were the most suggestive results
eNaughton protocol is a maximal exercise treadmill test