Table 2.

Association results between the selected SNP/metabolic pathway and % reduction in pain by therapy type in the discovery cohort.

Gene or metabolic Pathway	SNP rsID	Genotype frequency			Morphine		Nortriptyline		Drug Combination
		f(AA)	f(Aa)	f(aa)	β (SE)	P-value	β (SE)	P-value	β (SE)	P-value
OPRM1 gene	rs1799971	0.77	0.07	0.16	−0.97 (9.18)	0.999	2.15 (9.14)	0.988	−5.51 (9.18)	0.854
COMT metabolism	0 LPS (n = 5)				−7.13 (42.9)	0.973	−0.33 (42.9)	1.000	5.03 (42.9)	0.989
	1 LPS (n = 17)				−32.2 (41.9)	0.504	−28.9 (41.8)	0.555	−18.3 (41.9)	0.737
	2 LPS (n = 3)				−35.8 (49.3)	0.600	−46.6 (49.3)	0.507	−28.4 (49.3)	0.705
Serotonin receptor	rs6313	0.35	0.38	0.27	−0.88 (8.14)	0.999	2.12 (7.96)	0.985	−2.33 (8.15)	0.981
	rs7997012	0.54	0.42	0.04	2.92 (11.5)	0.986	−2.38 (11.5)	0.992	8.26 (11.5)	0.786
ABCB1 gene	rs1045642	0.23	0.54	0.23	14.5 (8.33)	0.193	18.2 (8.13)	0.065	32.5 (8.33)	4.89e-05*
	rs2032582	0.35	0.50	0.15	−13.4 (9.11)	0.307	−14.4 (9.10)	0.253	−21.2 (9.11)	0.052
CYP2C19 metabolism	PM (n = 0)				NA	NA	NA	NA	NA	NA
	IM (n = 3)				−30.4 (46.7)	0.586	−14.6 (46.7)	0.838	−8.50 (46.7)	0.939
	EM (n = 11)				−0.54 (51.1)	1.000	0.46 (51.1)	1.000	5.74 (51.1)	0.993
	UM (n = 11)				−27.2 (44.8)	0.624	−34.5 (44.6)	0.512	−20.8 (44.8)	0.729
CYP2D6 metabolism	PM (n = 1)				25.8 (46.9)	0.833	19.8 (46.9)	0.911	−1.90 (46.9)	1.000
	IM (n = 1)				23.2 (53.2)	0.886	−20.1 (53.2)	0.919	−3.46 (53.2)	0.999
	EM (n = 23)				−35.7 (44.9)	0.473	−45.0 (44.9)	0.355	−50.6 (44.9)	0.295
	UM (n = 0)				NA	NA	NA	NA	NA	NA

The results are based on linear mixed-effect models fitted to % reduction in pain with age, sex, treatment type, genetic factor, and an interaction between treatment type and genetic factor. A: major allele, a: minor allele. LPS: Low Pain Sensitivity; PM= poor metabolizers; IM= intermediate metabolizers; EM= extensive metabolizers and UM= ultra-rapid metabolizers.

^*Statistical significant set at α=6.25e-03 level.