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. 2022 Feb 10;12:820214. doi: 10.3389/fphar.2021.820214

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.