Association study between COMT, DRD2, and DRD3 gene variants and antipsychotic treatment response in Mexican patients with schizophrenia

Figures & data

Table 1 Clinical and demographic characteristics of the sample

Characteristics	Responders (n=88)		Resistance to treatment (n=49)		Ultra-resistance (n=33)		Statistics
	N	%	n	%	N	%
Gender							χ^2=1.19, df=1, P=0.551
Male	60	68	32	65	19	58
Female	28	32	17	35	14	42
Marital status							χ^2=3.35, df=1, P=0.187
Without partner	73	83	46	94	29	88
With partner	15	17	3	6	4	12
Occupation							χ^2=34.06, df=3, P=0.27
Unemployed	34	39	32	65	30	91
Housekeeping	15	17	2	4	2	6
Student	7	8	6	12	0	0
Employed	32	36	9	19	1	3
	Mean	SD	Mean	SD	Mean	SD	Statistics
Age (years)	38.3	10.3	37.9	9.8	43.6	12.8	F=3.416, df=167, P=0.035
Education (years)	9.8	2.8	11.3	2.6	11.5	2.7	F=6.625, df=167, P=0.002
Age of onset (years)	23.7	6.8	20.4	4.9	19.8	4.0	F=5.51, df=114, P=0.005
DUP (weeks)	53.1	65.3	72.7	64.9	88.4	56.6	F=4.13, df=167, P=0.018
Time evolution (weeks)	738.3	396.0	924.8	462.5	1,193.5	568.9	F=3.57, df=114, P=0.033
ED chlorpromazine (mg/d)	322.0	242.4	508.8	241.8	723.4	300.0	F=31.35, df=167, P<0.001

Abbreviations: DUP, duration of untreated psychosis; ED, equivalent doses.

Table 2 Genotype and allele frequencies of DRD2, COMT, and DRD3 genes

Gene polymorphism	Genotype frequencies			Allele frequencies
DRD2/A-241G (rs1799978)	AA	AG	GG	A	G
Responders (n=93)	61 (0.66)	16 (0.17)	16 (0.17)	138 (0.74)	48 (0.26)
Resistance to treatment (n=46)	24 (0.52)	5 (0.11)	17 (0.37)	53 (0.58)	39 (0.42)
Ultra-resistance (n=34)	27 (0.75)	4 (0.17)	3 (0.08)	58 (0.85)	10 (0.15)
DRD2/C376G (rs6279)	CC	CG	GG	C	G
Responders (n=78)	38 (0.49)	32 (0.41)	8 (0.10)	108 (0.69)	48 (0.31)
Resistance to treatment (n=39)	18 (0.46)	16 (0.41)	5 (0.13)	52 (0.67)	26 (0.33)
Ultra-resistance (n=29)	13 (0.45)	15 (0.52)	1 (0.03)	41 (0.71)	17 (0.29)
DRD2/C939T (rs6275)	CC	CT	TT	C	T
Responders (n=58)	12 (0.21)	27 (0.46)	19 (0.33)	51 (0.44)	65 (0.56)
Resistance to treatment (n=39)	6 (0.15)	16 (0.41)	17 (0.44)	28 (0.36)	50 (0.64)
Ultra-resistance (n=29)	1 (0.04)	14 (0.48)	14 (0.48)	16 (0.28)	42 (0.72)
DRD2/Taq1A (rs1800497)	CC	CT	TT	C	T
Responders (n=78)	20 (0.26)	37 (0.47)	21 (0.27)	77 (0.50)	79 (0.50)
Resistance to treatment (n=51)	16 (0.31)	24 (0.47)	11 (0.22)	56 (0.55)	46 (0.45)
Ultra-resistance (n=33)	7 (0.21)	18 (0.55)	8 (0.24)	32 (0.48)	34 (0.52)
COMT/Val158Met (rs4680)	Val/Val	Val/Met	Met/Met	Val	Met
Responders (n=81)	38 (0.47)	30 (0.37)	13 (0.16)	106 (0.65)	56 (0.35)
Resistance to treatment (n=45)	17 (0.38)	17 (0.38)	11 (0.24)	51 (0.57)	39 (0.43)
Ultra-resistance (n=32)	8 (0.25)	11 (0.35)	13 (0.40)	27 (0.42)	37 (0.58)
DRD3/Ser9Gly (rs6280)	Ser/Ser	Ser/Gly	Gly/Gly	Ser	Gly
Responders (n=95)	54 (0.58)	34 (0.34)	7 (0.08)	142 (0.75)	48 (0.25)
Resistance to treatment (n=45)	23 (0.51)	21 (0.47)	1 (0.02)	67 (0.74)	23 (0.26)
Ultra-resistance (n=36)	12 (0.33)	23 (0.64)	1 (0.03)	47 (0.65)	25 (0.35)

Table 3 Frequency of Gly carriers of DRD3 gene

Phenotype	Gly carriers	Non-Gly carriers
Responders (n=95)	41 (0.44)	54 (0.58)
Resistance to treatment (n=45)	22 (0.49)	23 (0.51)
Ultra-resistance (n=36)	24 (0.67)	12 (0.33)

Notes: Non-Gly carriers = Ser/Ser.Gly carriers = Gly/Gly, Ser/Gly.

Table 4 Logistic regression models for the prediction of resistance to treatment

Model	β	SD β	(β) Exp	CI 95% (β) Exp	P-value
Initial model: genetic factors
DRD3 Ser/Gly	0.64	0.32	1.90	1.0–3.6	0.048
COMT Met/Met	0.86	0.39	2.38	1.1–5.1	0.026
COMT Met/Met	0.83	0.41	2.30	1.03–5.17	0.042
Final model: genetic and clinical factors
Younger age of illness onset	0.91	0.35	2.49	1.24–4.97	0.010
Longer duration of untreated psychosis	0.008	0.003	1.008	1.002–1.014	0.010