TABLE 3.
Important pharmacogenetic markers in treatment of acute primary headaches.
| Drug group | Example(s) of drug(s) | SNP | Therapeutic effect (1) | Effect on safety | Affected molecule |
|---|---|---|---|---|---|
| NSAIDs | Diclofenac | CYP2C8*3 and CYP2C9*2,*3 | Higher effect in migraine Blanco et al. (2008), Dorado et al. (2008), Figueiras et al. (2016), Zajic et al. (2019) | Hepatotoxicity gastrointestinal bleeding Blanco et al. (2008), Figueiras et al. (2016), Zajic et al. (2019), McEvoy et al. (2021) | Lower activity of CYP2C8, CYP2C9 Blanco et al. (2008), Dorado et al. (2008), Figueiras et al. (2016), Zajic et al. (2019) |
| Ibuprofen | |||||
| Naproxen | |||||
| Ketorolac | |||||
| Ketoprofen | |||||
| — | — | PTGS2 rs20417 | — | Rectal cancer risk Makar et al. (2013) | COX-2 Makar et al. (2013) |
| — | Diclofenac | UGT2B7*2 | — | Hepatotoxicity gastrointestinal bleeding Daly et al. (2007) | Lower activity of UGT Daly et al. (2007) |
| Antiplatelet agents | Aspirin | PTGS1 rs117122585 | Decrease or abolished effects Marjan et al. (2014) (in silico prediction) | — | COX-1 Marjan et al. (2014) |
| — | — | CEP68 gene rs7572857G > A | — | Increased risk for aspirin-associated asthma Kim et al. (2010a) | Centrosomal protein of 68 kDa in length Kim et al. (2010a) |
| Opioid analgesics | Tramadol | OCT1*3-*6 | — | Higher risk for nausea, vomiting Tzvetkov et al. (2011) | OCT1 uptake strongly reduced or abolished Tzvetkov et al. (2011) |
| — | — | CYP2D6 gene duplication allele *1x2, *2x2, *35x2, *41x2 (UMs) | — | Sedation, nausea miosis increased risk for addiction Kirchheiner et al. (2008) | Higher activity of CYP2D6 Kirchheiner et al. (2008) |
| — | — | CYP2D6 *3, *4, *5, *6 (PMs) | Lower effect in migraine (Kirchheiner et al., 2008) | — | lower activity of CYP2D6 (Kirchheiner et al., 2008) |
| — | — | OPRM1 (118A > G) | Lower effect of pain therapy Stamer et al. (2016), (in vivo and in vitro) | Higher or lower doses of opioids may be needed to achieve same effect Stamer et al. (2016) | Changes in affinity of μ opioid receptor Stamer et al. (2016) |
| — | Butorphanol | COMT rs4680 | Increase pressure pain threshold with AG genotype of OPRM1 A118G Mura et al. (2013) | — | changes in affinity of μ opioid receptor Mura et al. (2013) |
| Ergot derivatives | Ergotamine Dihydroergotamine | near TSPAN2 rs12134493 | Lower effect in migraine without aura Moubarak and Rosenkrans, (2000) | Adverse effects not identified Moubarak and Rosenkrans, (2000) | TSPAN2 Moubarak and Rosenkrans (2000),Fang et al. (2018) |
| Triptans | Sumatriptan Zolmitriptan Eletriptan Naratriptan | CYP1A2 -163A | — | Higher risk of abuse Gentile et al. (2010) | Higher activity of CYP1A2 Gentile et al. (2010) |
| — | Triptans (unspecified) | GNB3 gene C825CC | Lower treatment effect in cluster headache Schürks et al. (2007),Gentile et al. (2010) | — | The G protein beta3 subunit Gentile et al. (2010) |
| — | Sumatriptan Zolmitriptan Eletriptan Naratriptan | C939T | Negative response to triptans in migraine Ishii et al. (2012) | — | DRD2 Ishii et al. (2012) |
| — | Eletriptan Rizatriptan Sumatriptan Frovatriptan Almotriptan Zolmitriptan | SLC6A4 STin2 VNTR | Inconsistent response to triptans in migraine Terrazzino et al. (2010) | — | Serotonin transporter Terrazzino et al. (2010) |
| — | Triptans (unspecified)s | PRDM16 rs2651899 | Higher effect in migraine Christensen et al. (2016) | — | PR domain Christensen et al. (2016) |
NSAIDs: Nonsteroidal anti-inflammatory drugs; CYP450: Cytochrome P; COX: Cyclooxygenase; UGT: Uridine 5′-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase); OCT1: Organic cation transporter 1; TSPAN2: tetraspanin 2; DRD2: dopamine receptor 2; TTH: Tension-type headache.