Mu opioid receptor (OPRM1) as a predictor of treatment outcome in opiate-dependent individuals of Arab descent

Figures & data

Figure 1 Flow chart of subjects, treatment approach, and outcome measures.

Abbreviations: ASI, The Addiction Severity Index; DSM-IV, The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.

Table 1 List of SNPs within the OPRM1 gene, their positions, and genotyping data based on the whole cohort (N = 183)

SNP_ID	Chr position^a	SNP	SNP gene location	Discrepancy rate^b	Call rate^c
rs6912029	154,402,201	G > T	Upstream (5′-UTR)	0.00%	100%
rs12205732	154,400,626	A > G	Upstream (5′-UTR)	0.00%	100%
rs1799971	154,402,490	A > G	Exon 1	0.00%	100%
rs510769	154,403,712	A > G	Intron 1	0.00%	100%
rs511435	154,410,240	A > G	Intron 1	0.00%	100%
rs524731	154,416,785	C > A	Intron 1	0.05%	99%
rs3823010	154,420,845	A > G	Intron 1	0.00%	100%
rs1381376	154,434,951	A > G	Intron 1	0.00%	100%
rs3778151	154,435,373	C > T	Intron 1	0.00%	100%
rs563649	154,449,660	A > G	Exon 2	0.00%	100%
rs2075572	154,453,697	C > G	Intron 2	0.00%	100%
rs540825	154,456,139	T > A	Intron 3	0.07%	99%
rs675026	154,456,256	G > A	Intron 3	0.12%	99%
rs562859	154,456,266	A > G	Intron 3	0.25%	99%
rs548646	154,459,840	A > C/G > T	Intron 3	0.52%	97%
rs648007	154,464,304	C > T	Intron 3	0.00%	100%
rs9322447	154,466,013	G > A	Intron 3	0.00%	100%
rs609148	154,472,707	C > T	Intron 3	0.07%	99%
rs606148	154,477,679	G > T	Intron 3	0.00%	100%
rs632395	154,478,944	C > T	Intron 3	0.00%	100%
rs648893	154,480,321	C > T	Intron 3	0.07%	99%
rs671531	154,482,434	A > G	Downstream (3′-UTR)	0.00%	100%

Notes:

a Chromosome positions are based on NCBI Human Genome Assembly Build 36.3;

b ratio of the number of discordant genotypes to the number of duplicates;

c ratio of the number of valid genotypes to the number of subjects genotyped (N = 183) at each locus.

Abbreviations: 3′-UTR, 3′ untranslated region; 5′-UTR, 5′ untranslated region.

Table 2 Details of the 183 opiate-dependent patients classified into three groups

Category	Subcategory	Good responders	Moderate responders	Poor responders	P value^f
Demographics	Patients (n, %)	(66/183) 36%	(32/183) 18%	(85/183) 46%
	Age^a [years]	31.0 [7.64]	33.1 [9.64]	34.5 [8.68]	0.0469^g
	Marital (single, married, divorced) (%)	(47%, 53%, 0%)	(47%, 50%, 3%)	(24%, 72%, 5%)	0.0055^h
	Education (%)	26%	16%	20%	0.4770^i
	Employment (%)	33%	31%	44%	0.3120^i
	Children (%)	41%	44%	75%	<0.0001^i
	Family with history of drug use (%)	21%	31%	20%	0.4110^i
Nicotine status	Nicotine (%)	80%	94%	82%	0.1830^i
	Age^a when start smoking [years]	13.1 [7.33]	14.6 [5.00]	12.9 [6.99]	0.4880^g
	Nicotine cigarette per day^a (#)	23.9 [18.30]	34.8 [16.70]	29.6 [21.80]	0.0304^g
Opiate consumption	Beginning taken amount^a (grams per day)	0.495 [0.27]	0.362 [0.215]	0.864 [2.67]	0.3030^g
	Last taken amount^a (grams per day)	0.996 [0.67]	0.86 [0.52]	1.43 [0.81]	<0.0001^g
Other drug use^b	Alcohol (%)	61%	53%	67%	0.3590^i
	Cocaine (%)	3%	3%	2%	1.0000^h
	Benzodiazepines (%)	55%	31%	68%	0.0014^i
	Amphetamine (%)	14%	28%	8%	0.0203^i
	Cannabis (%)	56%	31%	60%	0.0184^i
Opiate dependence	Age^a first opiate use (years)	22.1 [6.51]	22.8 [7.08]	22.3 [6.08]	0.8850^g
	Age^a of onset (years)	24.6 [6.68]	24.7 [7.64]	23.8 [6.76]	0.7150^g
	Duration of opiate use^a (years)	6.02 [3.48]	7.62 [4.96]	11.9 [6.9]	<0.0001^j
Drug screening	Positive admit UDS^c (%)	0%	0%	98%	<0.0001^i
Medical history^d	Overdose (%)	34%	44%	53%	0.0657^i
	Hepatitis (C virus infectious)	5%	6%	2%	0.5750^i
Psychiatric status^d	Impulsive (%)	91%	84%	98%	0.0330^i
	Suicide attempts (%)	33%	41%	54%	0.0349^i
	Depression (%)	3%	38%	16%	<0.0001^i
	Anxiety (%)	98%	100%	100%	0.5360^h
	Craving (%)	35%	62%	71%	<0.0001^i
	Euphoria (%)	50%	38%	78%	<0.0001^i
Hospitalization^g	Number^a of drug treatments	2.6 [1.87]	2.3 [1.42]	2.5 [1.78]	0.6630^g
	Number^a of detoxification treatments	2.6 [1.89]	2.3 [1.44]	2.5 [1.78]	0.6660^g
	Number^a of rehabilitation treatments	2.9 [2.02]	2.5 [1.46]	2.8 [1.97]	0.6250^g
	Number^a of counseling sessions	14.3 [11.00]	12.0 [11.10]	13.5 [10.90]	0.6290^g
	Number^a of self-help groups	14.3 [11.00]	11.4 [11.00]	13.4 [11.10]	0.4810^g

Notes:

a Standard deviation in square brackets;

b regardless whether prescribed or not as determined by substance screening tests at treatment entry;

c UDS: Urine Drug Screens at follow-up treatment;

d as obtained from their medical records at baseline;

e accumulative months of hospitalization treatment for psychiatric morbidity;

f statistically significant if P < 0.05; the bold-faced P-values are those that are significant;

g ANOVA f-test;

h Fisher exact test;

i Pearson’s Chi-squared test.

j Kruskal-Wallis test.

Table 4 Association of OPRM1 SNPs with treatment outcome

SNP_ID/genotype	Good responders	Moderate responders	Poor responders	P value
rs6912029
GG	34%	18%	48%	0.0329^a
GT	100%	0%	0%
TT	0%	0%	0%
rs12205732
GG	35%	18%	47%	0.0333^a
AG	100%	0%	0%
AA	0%	0%	0%
rs1799971
GG	33%	0%	67%	0.5440^b
AG	43%	18%	39%
AA	34%	18%	48%
rs510769
GG	36%	15%	48%	0.6040^b
AG	37%	22%	41%
AA	17%	17%	67%
rs511435
GG	38%	15%	47%	0.4740^b
AG	33%	24%	43%
AA	17%	17%	67%
rs524731
AA	17%	17%	67%	0.4400^b
AC	32%	25%	43%
CC	38%	15%	47%
rs3823010
GG	37%	16%	47%	0.8000^a
AG	33%	23%	43%
AA	25%	25%	50%
rs1381376
GG	36%	16%	48%	0.7600^a
AG	34%	24%	41%
AA	25%	25%	50%
rs3778151
CC	25%	25%	50%	0.8980^a
CT	36%	21%	42%
TT	36%	16%	47%
rs563649
GG	36%	17%	47%	0.9550^b
AG	35%	19%	45%
AA	0%	0%	0%
rs2075572
GG	42%	8%	50%	0.5080^b
GC	32%	20%	48%
CC	38%	19%	43%
rs540825
TT	38%	8%	54%	0.2440^b
TA	39%	11%	50%
AA	33%	23%	44%
rs675026
CC	35%	21%	44%	0.6940^b
CT	38%	16%	46%
TT	33%	10%	57%
rs562859
GG	35%	9%	57%	0.6690^b
AG	37%	16%	47%
AA	35%	21%	44%
rs548646
CC	33%	22%	46%	0.6360^b
CT	38%	17%	45%
TT	35%	9%	57%
rs648007
CC	33%	22%	46%	0.6310^b
CT	38%	16%	46%
TT	35%	9%	57%
rs9322447
GG	41%	17%	41%	0.2300^b
AG	29%	22%	49%
AA	44%	9%	47%
rs609148
CC	32%	23%	45%	0.2220^b
CT	41%	11%	48%
TT	40%	7%	53%
rs606148
GG	36%	16%	48%	0.4040^a
GT	38%	25%	38%
TT	0%	50%	50%
rs632395
CC	36%	16%	47%	0.6620^a
CT	36%	21%	43%
TT	0%	50%	50%
rs648893
CC	47%	7%	47%	0.2510^b
CT	39%	11%	50%
TT	33%	23%	44%
rs671531
GG	34%	21%	45%	0.5770^b
AG	36%	18%	46%
AA	39%	7%	54%

Notes:

a Fisher’s exact test;

b Pearson’s Chi-squared test.

Abbreviation: SNP, single nucleotide polymorphism.

Table 3 Differences in genotyping distribution of OPRM1 SNPs with frequency of opiate use

Variable	SNP_ID	P value
Frequency of opiate use (mean: 3.6 [0.8])	rs6912029	1.000
	rs12205732	1.000
	rs1799971	0.827
	rs510769	0.338
	rs511435	0.422
	rs524731	0.327
	rs3823010	0.303
	rs1381376	0.391
	rs3778151	0.292
	rs563649	0.165
	rs2075572	0.011
	rs540825	0.045
	rs675026	0.129
	rs562859	0.090
	rs548646	0.067
	rs648007	0.063
	rs9322447	0.038
	rs609148	0.028
	rs606148	0.263
	rs632395	0.201
	rs648893	0.014
	rs671531	0.032

Notes: Fisher’s exact test (P value < 0.05 is significant).

Abbreviation: SNP, single nucleotide polymorphism.