Table 1.

SNPs associated with nonopioids and opioids and its clinical consequences in pain management

Drug	Genotype/SNP	Clinical consequences	Reference
Metabolizing enzyme: CYP2D6
Codeine	Poor metabolizer	Lack of efficacy	[9,10]
	CYP2D6*3, CYP2D6*4, CYP2D6*5,
	CYP2D6*6, CYP2D6*7, CYP2D6*8,
	CYP2D6*11
	Ultrarapid metabolizer	Increased toxicity
	CYP2D6*1xn
	CYP2D6*2xn
Tramadol	Poor metabolizer	Reduced analgesia and increased risk of side effects	[11]
	CYP2D6*3, CYP2D6*4, CYP2D6*5,
	CYP2D6*6
	Ultrarapid metabolizer	Increased toxicity
	CYP2D6*1xn
	CYP2D6*2xn
Oxycodone	Poor metabolizer	Decreased response and lack of efficacy	[12]
	CYP2D6*3, CYP2D6*4, CYP2D6*5,
	CYP2D6*6
	Ultrarapid metabolizer CYP2D6*1xn	Increased metabolism and high risk of toxicity/side effects
	CYP2D6*2xn
Methadone	CYP2D6*10, CYP2D6*87, CYP2D6*89,	Decreased analgesia and/or increased toxicity	[13]
	CYP2D6*90, CYP2D6*93, CYP2D6*95,
	CYP2D6*97, CYP2D6*98
Metabolizing Enzyme: CYP2C9
NSAIDs, celecoxib, diclofenac	CYP2C9*2	Increased risk of GI bleeding	[14]
	CYP2C9*3
Cyclooxygenases 1: PTGS1
NSAIDs	PTGS1 (4331 A>T) PTGS1 4331T variant allele	Increased risk of acute coronary syndrome	[15]
Cyclooxygenases 2: PTGS2
Rofecoxib	PGTS2 (−765G>C) PGTS2-765C variant allele	Poorer pain relief	[16]
Opioid receptor µ: OPRM1
Morphine	OPRM1 118A>G	Needs larger doses of morphine for pain control	[17]
	Mutant 118G allele
Opioid receptor kappa: OPRK1
Morphine	OPRK1 (36 G>T)	Increased dose escalation of morphine is required in cancer related pain	[18]
Opioid receptor delta: OPRD1
Opioids	OPRD1 921T>C	Increased risk of opioid dependence in variant allele of OPRD1	[19,20]
Others: Phospholipase C gamma 1 (plus strand)
Acetaminophen and diclofenac, aspirin, propionic acid derivatives or pyrazolones	PLCG1 Ser 279 Gly	Increased risk of angioedema	[21]
HLA-DQB1
Acetaminophen	HLA-DQB1*02:02	Increased risk of cutaneous adverse reactions	[22]

SNP: Single-nucleotide polymorphism, CYP2D6: Cytochrome P450 2D6, CYP2C9: Cytochrome P450 2C9, NSAIDs: Nonsteroidal anti-inflammatory drugs, PTGS: Prostaglandin-endoperoxide synthase, HLA-DQB1: Major histocompatibility complex, class II, DQ beta 1, GI: Gastrointestinal